The enzymes, volume 37

Academic Press is an imprint of Elsevier 225 Wyman Street, Waltham, MA 02451, USA 525 B Street, Suite 1800, San Diego, CA 92101-4495, USA 125 London Wall, London, EC2Y 5AS, UK The Boulevard, Langford Lane, Kidlington, Oxford OX5 1GB, UK First edition 2015 © 2015 Elsevier Inc All rights reserved No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, or any information storage and retrieval system, without permission in writing from the publisher Details on how to seek permission, further information about the Publisher’s permissions policies and our arrangements with organizations such as the Copyright Clearance Center and the Copyright Licensing Agency, can be found at our website: www.elsevier.com/permissions This book and the individual contributions contained in it are protected under copyright by the Publisher (other than as may be noted herein) Notices Knowledge and best practice in this field are constantly changing As new research and experience broaden our understanding, changes in research methods, professional practices, or medical treatment may become necessary Practitioners and researchers must always rely on their own experience and knowledge in evaluating and using any information, methods, compounds, or experiments described herein In using such information or methods they should be mindful of their own safety and the safety of others, including parties for whom they have a professional responsibility To the fullest extent of the law, neither the Publisher nor the authors, contributors, or editors, assume any liability for any injury and/or damage to persons or property as a matter of products liability, negligence or otherwise, or from any use or operation of any methods, products, instructions, or ideas contained in the material herein ISBN: 978-0-12-803876-5 ISSN: 1874-6047 For information on all Academic Press publications visit our website at store.elsevier.com CONTRIBUTORS Ruby John Anto Cancer Research Program, Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India Jayesh Antony Cancer Research Program, Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India Suresh Awale Frontier Research Core for Life Sciences, University of Toyama, Toyama, Japan Dominique Bernard-Gallon Department of Oncogenetics, Centre Jean Perrin—CBRV, and EA 4677 “ERTICA,” University of Auvergne, Clermont-Ferrand, France Yves-Jean Bignon Department of Oncogenetics, Centre Jean Perrin—CBRV, and EA 4677 “ERTICA,” University of Auvergne, Clermont-Ferrand, France Elena De Gianni Interdepartmental Center for Industrial Research, Alma Mater Studiorum-University of Bologna, Rimini, Italy Nasim Faridi Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Carmela Fimognari Department for Life Quality Studies, Alma Mater Studiorum-University of Bologna, Rimini, Italy Neel M Fofaria Department of Biomedical Sciences and Cancer Biology Center, Texas Tech University Health Sciences Center, Amarillo, Texas, USA Laurent Guy EA 4677 “ERTICA,” University of Auvergne, and Department of Urology, CHU Gabriel Montpied, Clermont-Ferrand, France Hamid Heidarzadeh Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Gaeălle Judes Department of Oncogenetics, Centre Jean Perrin—CBRV, and EA 4677 “ERTICA,” University of Auvergne, Clermont-Ferrand, France ix x Contributors Seher Karsli-Ceppioglu Department of Pharmaceutical Toxicology, Faculty of Pharmacy, Marmara University, Istanbul, Turkey; Department of Oncogenetics, Centre Jean Perrin—CBRV, and EA 4677 “ERTICA,” University of Auvergne, Clermont-Ferrand, France Sung-Hoon Kim Cancer Preventive Material Development Research Center, College of Korean Medicine, Department of Pathology, Kyung Hee University, Seoul, South Korea G Mohan Shankar Cancer Research Program, Division of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India Shuji Nakano Graduate School of Health and Nutritional Sciences, Nakamura Gakuen University, Johnan-ku, Fukuoka, Japan Ahmad Nasimian Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran Marjolaine Ngollo Department of Oncogenetics, Centre Jean Perrin—CBRV, and EA 4677 “ERTICA,” University of Auvergne, Clermont-Ferrand, France Mai Thanh Thi Nguyen Faculty of Chemistry, University of Science, Vietnam National University, Hochiminh City, Viet Nam Nhan Trung Nguyen Faculty of Chemistry, University of Science, Vietnam National University, Hochiminh City, Viet Nam Misaki Ono Graduate School of Health and Nutritional Sciences, Nakamura Gakuen University, Johnan-ku, Fukuoka, Japan Fre´de´rique Penault-LLorca Department of Oncogenetics, Centre Jean Perrin—CBRV, and EA 4677 “ERTICA,” University of Auvergne, Clermont-Ferrand, France Alok Ranjan Department of Biomedical Sciences and Cancer Biology Center, Texas Tech University Health Sciences Center, Amarillo, Texas, USA Abbas K Samadi Sanus Bioscience, San Diego, California, USA Sanjay K Srivastava Department of Biomedical Sciences and Cancer Biology Center, Texas Tech University Health Sciences Center, Amarillo, Texas, USA, and Cancer Preventive Material Development Research Center, College of Korean Medicine, Department of Pathology, Kyung Hee University, Seoul, South Korea Contributors xi Mikako Takeshima Graduate School of Health and Nutritional Sciences, Nakamura Gakuen University, Johnan-ku, Fukuoka, Japan Fuyuhiko Tamanoi Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California, USA S Zahra Bathaie Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran, and Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California, USA PREFACE In recent decades, the important role of phytochemicals in dietary and as a functional food as well as for therapeutic uses has attracted attention of a large number of scientists in different fields including molecular and cellular science, medical science, and food science In this (Volume 37) and previous (Volume 36) volumes of “The Enzymes,” we attempted to compile studies on these topics and to discuss the mechanism of action of the phytochemicals in both cancer prevention and cancer treatment Molecular mechanism of the anticancer effect of isoprenoids, polyphenols, and flavonoids was described in the previous volume In the current volume (Volume 37), we continued and expanded the discussion to include some other families of compounds including quercetin, withanolides, dihydrochalcones, isothiocyanates, phytoestrogens, and sulfur-containing compounds In Chapter 1, we summarized possible molecular mechanisms of anticancer compounds, especially phytochemicals and natural products Detailed discussion on the mechanisms involving specific compounds can be found in other chapters We hope that these discussions provide helpful guidelines for new researches on the mechanism of action of natural products We are grateful to the authors for providing excellent and informative chapters in a timely fashion We also thank Mary Ann Zimmerman and Helene Kabes of Elsevier for their guidance and encouragement during the preparation of this volume S ZAHRA BATHAIE FUYUHIKO TAMANOI June 2015 xiii CHAPTER ONE How Phytochemicals Prevent Chemical Carcinogens and/or Suppress Tumor Growth? S Zahra Bathaie*,†,1, Nasim Faridi*, Ahmad Nasimian*, Hamid Heidarzadeh*, Fuyuhiko Tamanoi† *Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran † Department of Microbiology, Immunology and Molecular Genetics, University of California, Los Angeles, California, USA Corresponding author: e-mail addresses: bathai_z@modares.ac.ir; zbatha2000@yahoo.com Contents Introduction Phytochemicals Application in Chemoprevention Strategies 2.1 Blocking Initiation/Reversing Promotion 2.2 Activating Phase II Detoxifying Enzymes 2.3 Prooxidant/Antioxidant Activities 2.4 Protection Against Radiation 2.5 Alteration in Signaling Pathways 2.6 Effect on Cell–Cell Adhesion Machinery 2.7 Induction of Epigenetic Changes Phytochemicals Usage as Chemotherapeutic 3.1 Inhibition of Enzymes 3.2 Direct Binding to Biomacromolecules 3.3 Epigenetic Alteration/Chromatin Modification 3.4 RNA Modulation 3.5 Autophagy and UPR 3.6 Apoptosis Induction 3.7 Cell Cycle Arrest 3.8 Inhibiting Angiogenesis 3.9 Adjuvant/Combinatorial Therapy Summary References 11 12 12 13 13 14 14 17 18 22 24 25 28 30 31 33 33 Abstract Phytochemicals are a powerful group of chemicals that are derived from natural resource, especially with plants origin They have shown to exhibit chemoprevention and chemotherapeutic effects not only in cell lines and in animal models of cancer The Enzymes, Volume 37 ISSN 1874-6047 http://dx.doi.org/10.1016/bs.enz.2015.06.003 # 2015 Elsevier Inc All rights reserved S Zahra Bathaie et al but also some of them are in the clinical trial phase I and II Despite numerous reports of these phytochemical effects on cancer, an overview of the mechanisms of their action and their effects on various cellular and molecular functions important in the inhibition of cancer progression has been lacking In this review, we attempt to catalogue various studies to examine the effect of phytochemicals in cancer initiation, promotion, signaling, and epigenetic changes Because of the numerous studies in these topics, we only pointed out to some examples in each section INTRODUCTION Cancer is a growing health problem around the world; particularly with the steady increase in life expectancy, rising levels of urbanization and industrialization, increasing the fast food consumption, and the subsequent changes in environmental conditions, including the lifestyle and production of various pollutions On World Cancer Day 2014, a new global cancer report was compiled by UN Agency, the International Agency for Research on Cancer (IARC), showing that as a single entity, cancer is the biggest cause of mortality worldwide with an estimated 8.2 million deaths from cancer in 2012 Thus, this report suggests that cancer is now the world’s biggest killer—with the number of cases set to explode in coming years In fact, World Health Organization (WHO) indicates a 70% increase over next 20 years in worldwide cancer cases Low- and middle-income countries are most at risk of cancer overwhelming their health systems and hindering economic growth, as they have the least resources and infrastructure to cope with the predicted levels of disease escalation Restrictions on alcohol and sugar need to be considered, say WHO scientists as there now exists a “real need” to focus on cancer prevention by tackling smoking, obesity, and drinking Compiled by IARC, The World Cancer Report series is recognized as an authoritative source of global perspective and information on cancer The first volume appeared in 2003 and the second in 2008 The third volume in the series was released in 2014 The concept of a “magic bullet” was popularized by “Paul Ehrlich” (March 14, 1854–August 20, 1915) a German physician and scientist, who worked in the fields of hematology, immunology, and chemotherapy He defined a “magic bullet” as an ideal therapeutic agent that would be created and killed only the organism targeting a disease He reasoned that if a compound could be made that selectively targeted a disease-causing organism, then it could be selectively delivered to that organism; this Phytochemicals Prevent Chemical Carcinogens compound or “magic bullet” could only kill the target organism This concept is now known as “targeted therapy” [1] Since there appears to be no “magic bullet” to treat a diverse type of cancer, it has been apparent that cancer risks can be reduced by eliminating or at least minimizing the exposure to known carcinogens [2] In 1981, Doll and Peto in a report based on the statistical and epidemiological data have announced that among all risk factors of cancer—tobacco, alcohol, occupation, and so on—about 35% (10–70%) of human cancer mortality is attributed to diet [3] Although, it is a wide range variant, but it indicates the importance of diet as a risk factor of cancer On the other hand, an inverse relationship between the risk of specific cancers and consumption of vegetables and fruits have been reported [2] These indicate the importance of Phyto products in diet and in the life Phytochemicals (“Phyto” is from the Greek word meaning plant) are nonnutritive components in the plant-based diet that possess substantial anticarcinogenic and antimutagenic properties [2] Phytochemicals have different roles in both cancer prevention and treatment Despite remarkable progress in understanding the carcinogenic process and devising preventive/therapeutic effects of phytochemicals, the mechanisms of action of most phytochemicals have not yet been fully understood Bioavailability, toxicity, pharmacodynamic, and pharmacokinetics of the plant components(s) should be investigated Oral consumption of some phytochemicals results in lower plasma/serum concentration The reasons for this include: low intestinal absorption, degradation by intestinal enzymes, and/or metabolization by phase I and/or II detoxifying enzymes For example, crocin intestinal absorption is low and most of the orally consumed crocin appeared in the feces of rats [4] In addition, it is degraded by the intestinal enzymes and after h of oral administration of crocin, crocetin was detected in the serum of human subject [5] Thus, oral administration of crocin may have low efficacy for therapeutic purposes, and it should be better that it is administered via injection [6] In addition, adverse (or side) effects of phytochemicals should be considered For example, there are several hundred published research articles and many review papers about the beneficial effects of resveratrol in various diseases, in both in vivo and in vitro studies [7–11] Resveratrol is the most important stilbene related to cancer, and it is present in the foods like peanuts, pistachios, grapes, red and white wine, blueberries, cranberries, and even cocoa and dark chocolate It possesses a natural antiproliferative activity, due to its role as a phytoalexin (plant antibiotic) It also increased the S Zahra Bathaie et al antitumor activity of several other drugs, such as rapamycin in breast cancer and gemcitabine in pancreatic cancer, both in vitro and in vivo [12] Resveratrol affects all three stages of carcinogenesis, including: tumor initiation, promotion, and progression It was found that it acts as an antioxidant and antimutagen, and induces phase II drug-metabolizing enzymes (antiinitiation activity) It also mediated anti-inflammatory effects and inhibited COX1 and hydroperoxidase functions, as well as both COX-2 and MM-92 expression It is a potent inhibitor of nuclear factor NF-κB activation in DMBA3-induced breast cancer in female Sprague-Dawley rats and other tumor types Treatment of human breast cancer MCF-7 cells with resveratrol, in addition to the suppression of NF-κB activation, inhibited proliferation at S/G2/M phase (antipromotion activity) Extensive in vitro studies also revealed multiple intracellular targets of resveratrol, which in addition to inflammation, cell growth, and proliferation affect other targets like apoptosis, angiogenesis, invasion, and metastasis Resveratrol induces human promyelocytic leukemia cell differentiation (antiprogression activity) It inhibited the development of preneoplastic lesions in carcinogentreated mouse mammary glands in culture and inhibited tumorigenesis in a mouse skin cancer model Several other known targets of resveratrol are including: tumor suppressor p53 and Rb4; cell cycle regulators, cyclins, CDKs, p21WAF1, p27KIP and INK, and the checkpoint kinases ATM/ ATR; transcription factors NF-κB, AP-1, c-Jun, and c-Fos; angiogenic and metastatic factors, VEGF, and matrix metalloprotease 2/9; and apoptosis and survival regulators, Bax, Bak, PUMA, Noxa, TRAIL, APAF, surviving, Akt, Bcl-2, and Bcl-xL In some conditions, it also exerts the prooxidant activity and cause oxidative DNA damage that may lead to cell cycle arrest or apoptosis [13–15] In contrast to the above-mentioned data, some papers also reported its adverse effects and show some hints about its application for chemoprevention or, even, its therapeutic effects in human subjects [16–21] The renal toxicity of resveratrol in rat has been observed at the dose of 3000 mg/kg BW5 per day, but the dose of 300 was not toxic [19] However, it has been reported that low concentration (5 mg/kg BW) of resveratrol promotes breast cancer in mice and has a role in metastasis Resveratrol (50 mg/kg BW) induced tumor growth in both MDA-MB-2316 Cyclooxygenase Matrix metalloprotease-9 7,12-dimethylbenz(α)anthracene Retinoblastoma Body weight Mammary carcinoma-derived cell Phytochemicals Prevent Chemical Carcinogens (ERαÀ, ERβ+) and MDA-MB-435 (ERÀ and highly aggressive) breast cancer cells Investigation of the role of resveratrol in breast cancer metastasis indicated the lung metastasis in mice bearing MDA-MB-231 tumor, while metastasis of lung, liver, kidney, and bone from mice bearing MDA-MB435 mammary tumors have been observed [18] Resveratrol also affects the endocrine function and accelerates development of MNU7-induced mammary carcinomas of female rat [20] Thus, resveratrol effect is dependent to both concentration and tumor type Since impressive numbers of positive results were published, more attention on its safety should be considered for clinical usage of resveratrol In the present chapter, regardless of the phytochemical type, we focus on molecular mechanisms involved in the prevention or therapeutic activities of phytochemicals Figure summarized the most important aspect of molecular mechanism of phytochemicals action Because of the considerable studies on the molecular mechanisms of many phytochemicals functions, and the extensive reviews presented by the experts in the volumes 36 and 37 of The Enzymes, we only presented here a few examples for each mechanism with the goal to provide a guidance to check for each phytochemical by researchers in the future PHYTOCHEMICALS APPLICATION IN CHEMOPREVENTION STRATEGIES While there is no “magic bullet” that can completely cure cancer, like many types of diseases, cancer might be prevented To achieve this purpose, all the risk factors should be recognized completely and avoided Without complete identification of risk factors, this type of prevention is difficult to implement For primary prevention, there is a need for large lifestyle changes, but this is not easy to implement The population-based studies indicated the potential of some macronutrients (like fibers) and micronutrients (for example, vitamins and some trace elements) in vegetables and fruits to reduce the risk of cancer While, some macronutrients like carbohydrates and lipids increase the risk of some diseases including cancer The most exciting results have been obtained with antioxidant vitamins and their precursors, as well as the components which N-methyl-N-nitrosourea 248 Senarisoy, M., 14–15 Sengupta, S., 52 Senovilla, L., 85 Sensintaffar, J., 81–83 Senthil Murugan, R., 26, 29 Senthilkumar, K., 13 Serini, S., 26 Serrano, M., 196–197 Sesto, M.F., 82t Seth, K., 183–184 Sethi, G., 80 Seufi, A.M., 52–53 Sgambato, A., 18 Shah, A., 74–75, 82t Shah, N., 74–75 Shahbazfar, A.A., Shaltiel, A., 79 Shamaun, S.S., 97 Shamim, U., 11 Shan, B.-E., 50 Shan, Y., 120–121, 183 Shandilya, A., 79, 81–83 Shang, X., 126 Shankar, G.M., 44–65 Shankar, S., 120–121, 126, 179–181 Shao, J., 172 Shapiro, T.A., 58, 112 Shariat, S.F., 201–202 Sharma, A., 12 Sharma, D., 74–76, 82t Sharma, P.R., 63 Sharma, S., 3–5 Sharma, V.M., 57–59, 60t, 62 Sharmila, G., 13 Sharoni, Y., 140–142, 158–159 Sharp, A., 176 She, Q.B., 146–147 Sheehy, N., 82t Shehzad, A., 12 Shen, C.C., 97, 179–182 Shen, F., 53–56 Shen, G., 76, 120–122, 126 Shen, J.C., 197 Shen, L., 172–173 Shen, M., 84–85 Shen, S.-C., 51 Shen, W., 174 Shen, Y., 120–121 Author Index Shen, Y.C., 28 Shena, H., 100–103, 103t Sheridan, J.P., 126 Sherr, C.J., 28–29 Shi, C., 84–85 Shi, G., 78–79 Shi, J., 23 Shi, T., 95–96 Shi, X., 59–62, 60t Shi, Y., 11, 21, 113–116 Shibata, K., 23–24 Shieh, P., 177 Shieh, W.L., 103t Shields, P.G., 112 Shimada, N., 123–124 Shimizu, H., 194 Shimizu, K., 97 Shimizu, T., 201–202 Shimizu, Y., 49 Shin, D.Y., 172–173 Shin, H.K., 121 Shin, J.A., 118 Shin, Y.K., 84 Shindou, H., 201–202 Shinojima, N., 24 Shinozaki, H., 13 Shirahatti, N., 77–78 Shishodia, S., 3–5, 82t Shnimizu, M., 158 Shohat, B., 79 Shoskes, D.A., 56–57 Shrestha, B.G., 76–77 Shu, L., 9–10, 19, 123–124 Shu, Y.J., 27 Shukla, Y., 183–184 Shvo, Y., 74–75 Shyamaladevi, C.S., 52–53 Si, L., 177 Si, P., 25 Siegel, R.L., 157, 194 Sies, H., 48 Sikka, S., 80 Silva, A.M., 103t Silverman, D.T., 169–171 Simon, H.-U., 58, 63–64 Simone, R.E., 145 Sims, M., 23 Simsek, B., 10 Author Index Sinden, R.R., 58 Singh, A.V., 177, 179–180, 183 Singh, C.K., 3–5 Singh, H.B., 122 Singh, J., 64, 76–77, 82t Singh, K.P., 120 Singh, N.K., 121 Singh, O., 57 Singh, P., 140–142 Singh, P.P., 63 Singh, R., 180 Singh, S.K., 74–75, 85–86 Singh, S.V., 74–76, 79–80, 82t, 85–86, 113–118, 120, 125, 171–173, 177, 179–181, 183–184 Singh, T., 19 Singh-Gupta, V., 202 Singletary, K.W., 120, 182, 198 Siveen, K.S., 80 Skanchy, D.J., 57–58 Skowronski, L., 117–118 Skubatch, M., 126 Sleder, K.D., 82t Slevin, M., 183–184 Slimani, N., 171 Sloane, B.F., 77–78 Slowing, K.V., 3–5 Smeal, T., 75 Smejkal, K., 97–100 Smith, A., 56 Smith, B.C., 48 Smith, L.S., 95–96 Smith, T.K., 122 Snuggs, M.B., 175–176 Soares Nda, C., 151–153 Sobolewski, M.D., 120 Solbiati, L., 25, 32 Somashekhar, M., 96–97 Somers-Edgar, T.J., 32 Son, Y.-O., 51 Sondhi, S.M., 64 Song, S.Y., 29–30 Song, Y., 174 Song, Z., 58 Sonnad, B., 96–97 Soon-Shiong, P., 95–96 Sowa, Y., 49 Speizer, F.E., 169–171 249 Spiegelman, D., 112 Spitzner, M., 80 Sreenivasan, S., 23 Sridar, C., 123–124 Srinivasan, C., 77–78 Srinivasan, N., 13 Srinivasan, S., 74–75, 82t, 85–86 Srivastava, R.K., 120–121, 126, 179–181 Srivastava, S.K., 112–127, 180–181 Stampfer, M.J., 112 Stanton, B., 58 Stapleton, P.L., 123–124 Stavast-Kooy, A.J., 184 Steck-Scott, S., 140 Steinhilber, D., 125 Steinkellner, H., 123–124 Stephenson, K.K., 112 Sternlicht, M.D., 153–154 Stetler-Stevenson, W.G., 153–154 Stewart, D., 76 Stewart, N.A., 117–118 Stoner, G.D., 123–124 Story, E.N., 141–142 Stoyanova, S., 57–58, 63–64 Strathmann, J., 126 Strebhardt, K., 2–3 Strom, A., 195–196 Stuart, E.C., 32 Sturmans, F., 169–171 Su, B.N., 76–77 Su, J., 174 Su, J.L., 172–173 Su, Q., 172–176 Su, T., 50–51 Su, Y.-H., 62–63 Su, Z.Y., 9–10, 19, 123–124 Subar, A., 112 Subar, A.F., 169–171 Subramanyam, D., 57–59, 60t, 62 Sudhir, S., 74 Suetomi, Y., 95–96 Suganya, S., 13 Sugden, B., 24 Suhartati, T., 103t Sukari, M.A., 97 Suksamrarn, A., 103t Suksamrarn, S., 103t Suman, S., 74–75 250 Sun, C., 49, 84–85, 120–121 Sun, D., 74–75, 81–84, 82t, 172 Sun, H.D., 100–103, 103t Sun, J., 59–62, 60t Sun, L., 84 Sun, Q., 19 Sun, Y., 84 Sun, Z., 115 Sundar, D., 79, 81–83 Sunil Kumar, G., 57–59, 60t, 62 Suppipat, K., 120–121 Surana, R., 80 Surh, Y.J., 3, 7, 10, 12–13, 175–176 Suri, K.A., 76–77, 82t Sutaria, D., 126 Suter, C.M., 19 Suzuki, K., 15, 204 Svehlikova, V., 123–124 Swami, S., 209, 210t Swamy, N., 113–114, 180 Swanson, C.A., 169–171 Swanson, G.M., 169–171 Swift-Scanlan, T., 77 Syah, Y.M., 103t Szarc vel Szic, K., 74–75 Szatrowski, T.P., 175 Szczepanski, M.A., 118 Sze, D.M., 12 Szekeres, T., 175 Szliszka, E., 200 T Tabata, M., 57–58, 62 Tahir, U., 25 Tai, A., 58, 62, 64 Tajima, K., 168–169 Tajmir-Riahi, H.A., 17–18 Takabayashi, A., 11, 27 Takabayashi, S., 115–116 Takada, Y., 3–5, 24, 82t Takagi, Y., 76–77 Takami, Y., 58, 62, 64 Takayama, H., 103t Takei, Y., 58 Takeshima, M., 140–160 Takesue, F., 10 Takeuchi, M., 58–59, 60t Takeya, K., 103t Author Index Takeyama, Y., 95–96 Takezaki, T., 168–169 Talalay, P., 9–10, 75–76, 112, 123–124 Talamini, R., 112, 168–169 Tamanoi, F., 2–33 Tan, A.C., 12 Tan, B.K., 80 Tan, H., 172–173, 175–176 Tan, T.H., 117–118 Tan, T.W., 174 Tanaka, T., 13, 158 Tanaka, Y., 51 Tang, C.H., 26–27 Tang, D.D., 77–78 Tang, F.Y., 140–141, 145–146, 148–150, 152–153, 155–156 Tang, H.L., 174 Tang, L., 30, 112, 122, 151–152 Tang, N.Y., 118 Tang, S.N., 126 Tang, S.S., 172–173 Tang, W., 3–5 Tang, Y., 146–147, 152–153, 172–173, 175–176 Tanigawa, S., 51–52 Taniguchi, M., 58–59, 60t Tarantilis, P.A., 17–18 Tarantino, U., 174 Tasawwar, B., 32 Tatematsu, N., 13 Tavakkol-Afshari, J., 25 Tavakoli Anaraki, N., Tavana, B., 81–83 Taylor, E.W., 12 Taylor, P.B., 97 Taysi, S., 12 Teiten, M.-H., 19, 23 Telang, N.T., 7–9 Tellier, C., 24–25 Tempero, M.A., 95–96 Teng, C.M., 28 Teodoro, A.J., 140–141, 145–146, 151–152, 159 Terauchi, M., 23–24 Terracciano, R., 82t Testolin, G., 141–142 Tetsu, O., 155–156 Tewary, P., 75 251 Author Index Tezuka, Y., 95–97, 104–105 Thaiparambil, J.T., 77–78, 82t Thakkar, A., 126 Thalmann, G.N., 203 Thangapazham, R.L., 12 Thao, L., 81–83 Thejass, P., 122, 174 Thi, P.H., 96–97 Thiele, C.J., 80 Thirumalai, K., 23 Thissen, M.R., 184 Thomas, C.F., 3–5 Thomas, C.L., 75 Thomas, G.J., 77–78 Thomet, O.A., 58, 63–64 Thompson, C.R., 75 Thomson, S.J., 118 Thornquist, M.D., 169–171 Ti, X., 23 Tian, D., 123–124 Tian, H., 177 Tian, H.Y., 95–96 Tian, R., 84–85 Tian, S., 77–78 Tickoo, S., 122 Tien, N., 119 Tighiouart, M., 77–78, 82t Tillement, J.P., 26–27 Tilli, C.M., 184 Tilstam, U., 57 Timmermann, B.N., 74–75, 79, 82t, 84–85 Tindall, D.J., 157 Tjonneland, A., 171 Toden, S., 23–24 Toksoz, D., 77–78 Toland, A.E., 205 Tollefsbol, T.O., 16, 19–21 Tombal, B., 194 Tome, M.E., 175 Tong, P., 184 Tong, X., 74–75 Tony Kong, A.N., 9–10 Topcu, Z., 14–15 Torre, L.A., 158 Torres, K., 82t Torres, M., 75 Torsello, A., 26 Torun, M., 10 Tosirisuk, V., 57–58, 62 Touchard, C., 76 Trachootham, D., 117–118, 180 Tracy, J.H., 123–124 Trakhtenberg, S., 171–172 Tram, L.H., 97 Tran, A.H., 96–97 Tran, S.H., 29 Trejo-Skalli, A.V., 77–78 Trejo-Solis, C., 140, 157 Trendowski, M., 77 Tresoldi, I., 174 Trichopoulos, D., 171 Trichopoulou, A., 171 Trieu, V., 95–96 Tromp, M.N., 47 Trucchi, B., 77–78 Trump, D.L., 172–173 Tsai, A.G., 47 Tsai, E.M., 29–30 Tsai, J.Y., 177 Tsai, K.S., 15, 28 Tsai, L., 77–78 Tsai, S.C., 122 Tsai, T.F., 114–115 Tsao, S.W., 177 Tse, A.K.-W., 50–51 Tseng, S.-Y., 58–59, 60t Tseng, T.H., 21, 26, 100–103, 103t Tsichlis, P.N., 199 Tsou, M.-F., 50, 119 Tsubura, A., 3–5 Tsuruo, T., 16 Tucker, A.M., 57 Tumino, R., 171 Turcatti, G., 75–76 Turnbull, C.I., 118 Tuveson, D.A., 95–96 Tzeng, C.W., 97 U Uchida, K., 28 Ucker, D.S., 124–125, 178–179 Udeani, G.O., 3–5 Uechi, G.T., 79, 82t Ueda, J.Y., 96–97 Ueda, S., 11, 27 Ueda, Y., 28 252 Uehara, N., 121 Ulbrich, H., 58, 63–64 Ulirsch, J., 77 Ullah, M.F., 11 Ullrich, A., 2–3 Um, H.J., 80, 82t Umezawa, K., 47–48 Upadhyay, S., 28–29 Urig, S., 181–182 Urooj, A., 106–107 Usha, S., 17–18 Ushio, S., 58–59, 60t, 64 Uyeda, M., 15 V Vacca, A., 85–86 Vaid, M., 19–22 Vaishampayan, U., 140–141, 145–146, 157–158 Vaissiere, T., 205 Valdes, J., 47 Valenzuela, A., 47 van Breemen, R.B., 76–77, 143–144 Van Camp, G., 74–75 Van De Waarsenburg, S., 53–56 van den Brandt, P.A., 169–171 Van der Veken, P., 79 van Hamont, J.E., 58 Van Lint, C., 82t van Poppel, G., 169–171 van Poppel, G.A., 169–171 Van Poppel, H., 194 Van Wesemael, K., 82t Vanden Berghe, W., 74–75, 79, 82t Vanden, B.W., 14 VandenBoom, T.G., 23 Vangeli, M., 32 Vardi, A., 206–207 Veech, R.L., 97 Veenstra, T.D., 182 Velmurugan, B., 152–153 Venema, R.C., 120 Venook, A.P., 95–96 Verhagen, H., 169–171 Verhoeven, D.T., 169–171 Vertino, P.M., 77–78, 82t Vidanes, G., 123–124 Vidya Priyadarsini, R., 26, 29 Author Index Vigilanza, P., 176–177 Vigo, J.S., 76–77 Vinci, M., 32 Vineis, P., 171 Vinyard, B.T., 122 Vishwakarma, R.A., 63 Visioli, F., 45–46 Vitale, I., 85 Vitalini, S., 45–46 Vogel, V.G., 172–173 Vogelstein, B., 52 Vogt, A., 116 Voinnet, O., 207–208 Volate, S.R., 52–53 Vollmar, A.M., 172–173, 184 Von Hoff, D.D., 95–96 Voorrips, L.E., 169–171 Votta, B.J., 97 Vowell, C.L., 79, 82t Vuerstaek, J.D., 184 W Wacholder, S., 169–171 Wade, K.L., 112 Wadhwa, R., 74–77 Waggoner, D., 18–19 Wahid, F., 12 Wahl, D., 3–5 Waisman, D.M., 77–78 Wajed, S.A., 206 Wakabayashi, N., 76 Walch, E.T., 26–27 Walczak, H., 126 Wali, A., 78–79 Wall, K.M., 52–53 Wallace, D.M., 52 Walters, D.G., 169–171 Wang, A.H.J., 97 Wang, B.W., 177 Wang, C., 57, 123–124, 168–169 Wang, F., 120, 183 Wang, G., 24 Wang, H., 25, 58–59, 60t, 95–96, 104 Wang, J., 59–62, 60t, 126 Wang, L., 51, 115, 118 Wang, L.-M., 51 Wang, M., 75, 84–85 Wang, M.H., 123–124 253 Author Index Wang, M.J., 179–182 Wang, M.-X., 50 Wang, M.Y., 120, 180 Wang, Q., 115–116 Wang, R., 120–121 Wang, S., 59–62, 60t, 82t, 116–117, 123–124, 198–199 Wang, T.T., 141–142 Wang, W., 117–118, 123–124 Wang, X., 51, 84–85, 117–118, 125–126, 143–144, 177, 182, 199 Wang, X.D., 144, 146–147 Wang, X.F., 125 Wang, X.H., 100–103, 103t Wang, Y., 57, 78–79, 97, 100–104, 103–104t, 126, 145 Wang, Z., 23–24, 31, 150, 184, 200–201 Wang, Z.-J., 49–50 Warburton, R., 77–78 Ward, E., 95–96 Wargovich, M.J., 52–53 Warin, R., 116 Watanabe, S., 195 Watkins, D.N., 120–121 Watson, W.H., 75 Wattenberg, L.W., 123–124 Weaver, L.M., 97 Weber, G., 53–56 Weber, M.J., 198 Wedig, T., 77–78 Wedlich, D., 155–156 Wei, D., 115 Wei, M.Y., 140 Wei, Y., 125 Wei, Y.-H., 49–50 Weigert, A., 125 Weinberg, M.S., 179–181 Weinberg, R.A., 77 Weinstein, I.B., 176–177 Weis, W.I., 13 Wells, T.N., 75–76 Wen, C.J., 22 Wen, J., 29–30, 172–173 Wen, L., 172–173, 175–176 Wen, S.Y., 126 Wendschlag, N., 77–78 Weng, D., 49 Weng, H., 27 Weng, Y.S., 174 Wenzel, U., 125 Werb, Z., 153–154 Werbovetz, K.A., 57–58 Werz, O., 63–64 Wexner, S.D., 56–57 Whitehead, J.P., 3–5 Whiteman, M., 171 Whitesell, L., 77–78, 83 Wicker, C.A., 126 Widodo, N., 76–77 Wienands, J., 80 Wierda, W.G., 180 Wiesmuller, L., 17–18 Wijeratne, E.M., 83 Wiktorska, K., 125–126 Wilchek, M., 176 Wilkinson, D.I., 15–16 Willett, W.C., 169–171 Williams, D.E., 112–114, 182 Williamson, G., 123–124 Wilson, T.A., 167–168 Win, M.N., 96–97 Wink, M., 16–17 Winnik, B., 121 Wipf, P., 79, 82t Wippich, P., 57–58, 63–64 Wise, L.A., 112 Wiseman, H., 195, 203–204 Wodarz, D., 23–24 Wolf, C.R., 76 Wolf, F.I., 18 Wolff, H.A., 80 Wolff, J., 79 Wolk, A., 198 Won, S.J., 103t Wong, R., 95–96 Wong, R.K., 30 Wong, Y.C., 177 Wood, T.E., 95–96 Wood, W.G., 50 Wouters, A., 74–75 Wright, S.E., 118, 180–181 Wu, B., 22 Wu, C., 23, 28 Wu, C.C., 76–77 Wu, C.-H., 57, 59, 60t Wu, C.L., 115–116, 180–182 254 Wu, D.M., 125 Wu, H., 126 Wu, J.M., 32 Wu, J.Y., 26–27 Wu, K., 120–121 Wu, L.X., 22 Wu, M.J., 77 Wu, M.Y., 125 Wu, P.-L., 57–59, 60t, 62 Wu, S.H., 118 Wu, S.J., 171 Wu, T.T., 203 Wu, T.X., 168–169 Wu, T.Y., 10 Wu, W., 78–79 Wu, W.J., 125 Wu, X., 115–116, 179–182 Wu, X.J., 172–173, 175–176 Wu, X.S., 27 Wu, X.T., 168–169 Wu, Y.-C., 50, 57, 59, 60t, 76–77 Wu, Y.-T., 57–59, 60t, 62 Wuerzberger-Davis, S., 79 Wuth, B., 182 X Xi, L., Xia, J., 3–5 Xia, Y., 52 Xiao, D., 114–118, 120, 122, 125, 172–173, 176–177, 179–181, 183–184 Xiao, H., 120, 179–181, 184 Xiao, J., 25 Xiao, K., 24 Xiao, Z., 117–118, 182 Xie, J., 77–78 Xie, Y., 59–62, 60t Xing, H., 49 Xu, C., 76, 120–124 Xu, K., 97, 103–104, 104t Xu, L., 95–96, 174, 203 Xu, M., 51, 84–85, 172–173 Xu, N., 172 Xu, R., 22 Xu, W.S., 20 Xu, Y.M., 83 Author Index Y Yagasaki, K., 153–154 Yagi, Y., 58, 62, 64 Yahara, S., 15 Yamamoto, I., 58, 62, 64 Yamamoto, M., 9–10, 76 Yamamoto, Y., 58–59, 60t Yamaoka, Y., 11, 27 Yamashita, M., 23–24 Yamauchi, M., 12 Yamazaki, H., 123–124 Yan, H., 115–116 Yan, J., 58–59, 60t, 63 Yan, S., 80 Yan, Z., 29, 49–50 Yance, D., 30 Yang, B.F., 125 Yang, C.H., 23 Yang, C.M., 156 Yang, C.S., 123–124 Yang, H.Z., 75, 78–79 Yang, J.-H., 49–50 Yang, J.-S., 17, 26–27, 50, 115–116, 118–119, 172–174, 180–182 Yang, K., 13 Yang, L., 30, 122 Yang, N., 24 Yang, P., 115–116 Yang, Q., 58–59, 60t, 63, 172 Yang, S.-H., 63 Yang, W., 32 Yang, Y., 63 Yang, Y.M., 123–124 Yang, Y.R., 180 Yang, Z., 79, 82t, 151–152 Yang, Z.Y., 112 Yao, S.Q., 172–173 Yao, X., 22 Yasuda, M., 10 Yates, N.A., 79, 82t Ychou, M., 95–96 Yco, L.P., 74–75, 80, 82t Ye, L., 121 Ye, M.X., 32 Yeh, R.D., 172–174 Yen, F.L., 97 Yen, H.-C., 63 Author Index Yi, L., 172–173, 175–176 Yin, R., 95–96 Yin, X.R., 174 Yin, Z., 84 Yip, H.-Y., 58–59, 60t Yokoi, T., 123–124 Yokoyama, M., 16 Yokoyama, S., 96–97 Yokoyama, T., 24 Yoon, K.-A., 52 Yoshida, R., 123–124 Yoshigae, Y., 123–124 Yoshihiro, A., 113–116 Yoshizawa, K., 121 Youn, Y.K., 121 Young, J.F., 48 Young, L.F., 26, 140–141, 145–146, 151–152 Young, P.J., 169–171 Yousuf, K., 75 Yu, C.S., 118, 174 Yu, D.Q., 75 Yu, H., 50–51, 80 Yu, J., 174 Yu, R., 123–125, 178–179 Yu, S., 123–124 Yu, S.-T., 58–59, 60t, 62 Yu, T.W., 120, 182 Yu, Y., 74–75, 81–84, 82t Yu, Z., 182 Yu, Z.-L., 50–51 Yuan, X., 122–124 Yuan, Y.Y., 19–20 Yue, J., 23 Yue, W., 177 Yun, C.H., 84 Yun, J., 104, 104t Yuri, T., 3–5 Yurnawilis, N.Aimi, 103t Z Zaăhner, H., 5758 Zaldivar, M., 7475 Zavaglia, C., 32 Zencir, S., 14–15 Zeng, X., 175–176 Zeng, Y., 179–181, 184 255 Zeng, Z.L., 125 Zhai, D., 174 Zhan, C.G., 74–75, 77–78, 81–83, 82t Zhan, X.H., 78–79 Zhang, C., 19, 59, 60t, 123–124 Zhang, C.L., 75 Zhang, D., 174 Zhang, H.Y., 59–62, 60t, 74–75, 82t, 95–96, 117–118, 125, 144, 180 Zhang, J., 10, 23, 80, 123–124 Zhang, L., 22–23, 57, 121 Zhang, L.L., 75, 77–79, 81–83 Zhang, M., 112 Zhang, Q., 24, 49–50 Zhang, R., 113–116 Zhang, T., 23, 74–75, 81–83, 82t Zhang, W., 180 Zhang, X., 10, 22, 58–59, 60t, 74–75, 79, 158 Zhang, X.H., 172 Zhang, Y., 11, 21, 31, 75–76, 112–113, 123–125, 172–174 Zhang, Y.K., 172 Zhang, Z., 51 Zhao, K., 172 Zhao, Q.S., 100–103, 103t Zhao, R., 56–57, 199 Zhao, X., 120–121 Zhao, X.-H., 49–50 Zhao, Y., 59, 60t Zhao, Y.L., 32 Zheng, B., 24 Zheng, J.N., 26–27 Zheng, L., 115 Zheng, M., 26–27 Zheng, W., 202–205 Zheng, X., 97, 103–104, 104t Zheng, Z.H., 27 Zhong, M., 172–173 Zhou, B., 49 Zhou, J., 172–173 Zhou, Q., 115–116 Zhou, T., 115–116 Zhou, W., 33 Zhou, X., 59–62, 60t, 64 Zhou, Y., 117–118, 168–169, 180 Zhu, B.Y., 172–173 256 Zhu, F., 84–85 Zhu, H., 9–10, 77–78 Zhu, Q.S., 82t Zhu, W., 126 Zhu, X., 58–59, 60t, 120–121 Zhu, Y., 115–116, 171, 177 Zhuang, J.X., 115–116 Zhuang, W., 24, 168–169 Zhub, G.F., 100–103, 103t Ziboh, V.A., 47–48 Ziegler, R.G., 169–171 Zini, R., 26–27 Author Index Zirpoli, G.R., 112 Zito, S.W., 97 Zohrabian, V.M., 51 Zou, J.-C., 58–59 Zou, P., 74–75, 81–83, 82t Zu, X.Y., 172–173 Zubair, H., 11 Zucchetto, A., 168–169 Zuryn, A., 118 Zwacka, R.M., 200 Zweier, J.L., 9–10, 52 Zwelling, L.A., 14 SUBJECT INDEX Note: Page numbers followed by “f ” indicate figures and “t ” indicate tables A Adjuvant/combinatorial therapy, 31–33 Allicin (154 μM), 174 Allium compounds apoptosis, animal models, 177 apoptosis, malignant cells, 172–177 vegetables, 168–169, 169f Allyl isothiocyanate (AITC) cancer cell progression, 122 cancer cells target, ITCs, 122–123 metastasis, 122 mitochondrial apoptosis, 122 sinigrin source, 122 toxicity studies, 122–123 in vivo studies, 122 Angiogenesis inhibition chemotherapeutics, phytochemicals usage, 30–31 soy phytoestrogens, 201–202 tryptanthrin, 64 Antiausterity activity, 104–106 Anticancer agent quercetin, 48–51 apoptosis, 50 cell cycle regulation, 49–50 tumor growth and invasiveness, 50–51 tryptanthrin, 60t tryptanthrin, properties, 58–62 withaferin A (WFA), 82t Anti-inflammatory activity lycopene, 144–145 quercetin, 51 tryptanthrin, 63–64 Antioxidant activity chemoprevention, phytochemicals application, 11 enzyme induction, 9–10 lycopene, 143–144 quercetin, 45–46 soy phytoestrogens, 203–205 tryptanthrin, 63 Antioxidant response elements (AREs), 75 Apoptosis induction allium compounds, animal models, 177 Brassica compounds, animal models, 183 chemotherapeutics, phytochemicals usage, 25–28 lycopene, 151–153 malignant cells, allium compounds, 172–177 Bcl-2 and MAPK family modulation, 172–174 microtubule alterations and calcium homeostasis changes, 176–177 p53 activation, 174 ROS generation, 175–176 signaling pathways, 173f malignant cells, Brassica compounds Bcl-2 and MAPK family modulation, 180 caspase activation, 180–181 histone deacetylase modulation, 182 intrinsic and/or extrinsic apoptotic pathway, 179–180 ITCs, proapoptotic activity, 178–179 microtubule alteration, 182 ROS generation, 181–182 signaling pathways, 179f mitochondrial, benzyl isothiocyanate, 115–116 quercetin, 50 soy phytoestrogens, 199–201 withaferin A (WFA), 76–77 Artocarpus altilis chemical constituents, 97 prenylated aurones, 100f prenylated dihydrochalcones, 99f prenylated flavonoids, 98f toxicology, 106–107 257 258 Ascorbic acid, 11 Ashwagandha, 74 See also Withaferin A (WFA) Autophagy, 24–25 See also Apoptosis 3-Azidowithaferin A (AzWA), 75 B Baicalin, 11 Bcl-2 modulation Allium compounds, apoptosis, 172–174 Brassica compounds, apoptosis, 180 Benzyl isothiocyanate (BITC) angiogenesis, 116 cancer cell progression, 114–115 metastasis, 116 mitochondrial apoptosis, 115–116 source, 113–114 toxicity, 117 in vivo studies, 116–117 Bioavailability and tissue distribution, lycopene, 141–143 Biomacromolecules, direct binding to, 17–18 Biosynthesis pathway, 97–100, 102f Blocking initiation/reversing promotion, 7–9 Brassica chemopreventive effects, 178 compounds apoptosis, animal models, 183 apoptosis in malignant cells, 178–182 vegetables, 169–171, 170f Breast cancer and lycopene, 158–159 Brussels See Brassica C Calcium homeostasis changes, Allium, 176–177 Camptothecin, 15 Cancer prevention and therapy, lycopene, 156–159 Cancer stem cells (CSCs), 85 Caspase activation, Brassica compounds, 180–181 β-Catenin, 13 Cell–cell adhesion machinery, 13 Subject Index Cell cycle regulation chemotherapeutics, phytochemicals usage, 28–30 lycopene, 148–151 quercetin, 49–50 soy phytoestrogens, 196–199 Chemoprevention strategies, phytochemicals application blocking initiation/reversing promotion, 7–9 cell–cell adhesion machinery, 13 epigenetic changes, 13–14 mechanisms of action, 6f phase II detoxifying enzymes activation, 9–10 population-based studies, 5–6 prooxidant/antioxidant activities, 11 protection against radiation, 12 ROS sources, 8f signaling pathways, alteration in, 12–13 Chemotherapeutics, phytochemicals usage adjuvant/combinatorial therapy, 31–33 angiogenesis inhibition, 30–31 apoptosis induction, 25–28 autophagy and UPR, 24–25 biomacromolecules, direct binding to, 17–18 cell cycle arrest, 28–30 enzyme inhibition, 14–15 epigenetic alteration/chromatin modification, 18–22 RNA modulation, 22–24 topoisomerases I/II, 14–15 Cisplatin, 85 Colon cancer cells (COLO 205), apoptosis, 172–173 COX-2 inhibitory activity, 63–64 Crocetin anticancer effect, 25 Cruciferous vegetables, 112 See also Brassica; Isothiocyanates (ITCs) Curcumin, 12 Cyclooxygenase-2 (COX-2) expression, 76–77 Cytoskeletal-directed agents, 77–78 Cytotoxicity, prenylated flavonoids, 100–103, 103t 259 Subject Index D H Daidzein, 195 Detoxifying enzymes activation, 9–10 Diallyl disulfide (DADS) (40 μM), apoptosis, 172–173 Diallyl sulfide (DAS) (40 μM), apoptosis, 172–173 Diallyl trisulfide (DATS) (40 μM), apoptosis, 172–173 Dimethoxycurcumin (DMC), 22 DNA methylation, 21–22, 205–207 Heat shock proteins, 81–84 Histone deacetylase modulation, 182 modifications, 20–21, 207 4-Hydroxywithanolide E (HWE), 83–84 E Enzyme inhibition, chemotherapeutics, 14–15 Epigenetics alteration/chromatin modification, 18–22 changes, phytochemicals application, 13–14 chemoprevention, phytochemicals application, 13–14 definition, 13–14 prostate cancer, soy phytoestrogens DNA methylation, 205–207 histone modifications, 207 miRNAs regulation, 207–209 telomerase activity, 15–17 Estrogenic activity, soy phytoestrogens, 195–196 F Flavonoids See Quercetin; Tryptanthrin 5-Fluorouracil, with sulforaphane, 125–126 Forkhead box protein (FOXO1), 114–115 Free radical scavenging activity, 47 G Galanals A and B, 28 Genistein, 195 Glucosinolates, 177–178 Glycitein, 195 Gossypol, 14 Growth factor modulation and receptor signaling, 146–148 I I3C10, 7–9 I3C97, 29 IκB kinase (IKK), 75–76 Indoleamine 2,3-dioxygenase (IDO) catalyzes, 84 International Agency for Research on Cancer (IARC), Intrinsic and/or extrinsic apoptotic pathway Brassica compounds, apoptosis, 179–180 Invasion and metastasis, lycopene, 153–156 Isoflavones See Soy phytoestrogens Isothiocyanates (ITCs), cancer cells cellular uptake mechanism, 124f chemopreventive effects, 113f, 123–125 chemotherapeutic targets, 114f combination therapy, 125–126 proapoptotic activity, Brassica compounds, 178–179 target allyl isothiocyanate, 122–123 benzyl isothiocyanate, 113–117 phenylisothiocyanate, 117–119 sulforaphane, 120–121 uptake, 112–113 ITCs See Isothiocyanates (ITCs), cancer cells L Lung cancer and lycopene, 159 Lycopene, 22 anti-inflammatory activity, 144–145 antioxidant activity, 143–144 bioavailability and tissue distribution, 141–143 and breast cancer, 158–159 cancer prevention and therapy, 156–159 invasion and metastasis, 153–156 and lung cancer, 159 and prostate cancer, 157–158 260 Lycopene (Continued ) source, 140, 142f target, 141f tumor-inhibitory activity, 145–153 apoptosis-inducing activity, 151–153 cell cycle progression, 148–151 growth factor modulation and receptor signaling, 146–148 M Magic bullet, 2–3 Mammalian target of rapamycin (mTOR), 114–115 Metabolic enzymes, 84 Metastasis inhibition, 202–203 MicroRNAs (miRNAs), 22–23 Microtubule alteration Allium compounds, apoptosis, 176–177 Brassica compounds, apoptosis, 182 miRNAs regulation, 207–209 Mitochondrial apoptosis, 115–116 Mitogen-activated protein kinase (MAPK) family modulation Allium compounds, apoptosis, 172–174 Brassica compounds, apoptosis, 180 Mitosis inhibition, 79 MMP-9, 115–116 Myricetin, 11 N Necroptosis See Apoptosis NFκB, 115 Nitric oxide inhibitory action, 47 Nrf-2, 76 P p53 activation, 174 influence, 51–52 Paclitaxel (taxol), 17 p53 activation, 174 3,3,4,5,7-pentahydroxyflavone See Quercetin Phase II detoxifying enzymes activation, 9–10 Subject Index Phenylisothiocyanate (PEITC) cancer cell progression, 118 clinical trail, 119 metastasis, 119 mitochondrial apoptosis, 118 source, 117–118 in vivo studies, 119 Phosphoinositide kinase (PI3K)/AKT pathway, 114–115 Phytochemicals See also Quercetin application, chemoprevention strategies blocking initiation/reversing promotion, 7–9 cell–cell adhesion machinery, 13 epigenetic changes, 13–14 mechanisms of action, 6f phase II detoxifying enzymes activation, 9–10 population-based studies, 5–6 prooxidant/antioxidant activities, 11 protection against radiation, 12 ROS sources, 8f signaling pathways, alteration in, 12–13 chemotherapeutics, usage in adjuvant/combinatorial therapy, 31–33 angiogenesis inhibition, 30–31 apoptosis induction, 25–28 autophagy and UPR, 24–25 biomacromolecules, direct binding to, 17–18 cell cycle arrest, 28–30 enzyme inhibition, 14–17 epigenetic alteration/chromatin modification, 18–22 RNA modulation, 22–24 oral consumption, resveratrol role, 3–5 roles, PI3K/Akt/mTOR pathway, 51 Prenylated aurones, 100f Prenylated dihydrochalcones antiausterity activity, 104–106 cytotoxicity, 103–104 Prenylated flavonoids Artocarpus altilis, 101f cytotoxicity, 100–103, 103t Prenylated phenolic compound, 97–100, 102f 261 Subject Index Programmed cell death See Apoptosis Prooxidant activities, 11 Prostate cancer, 194 and lycopene, 157–158 Proteasomal inhibition, 78–79 Q Quercetin action, cancers of various origin, 54t as anticancer agent, 48–51 apoptosis, 50 cell cycle regulation, 49–50 tumor growth and invasiveness, 50–51 anti-inflammatory agent, 51 antioxidative property, 45–46 biosynthesis, 45 chemical-induced tumor and xenograft, 52–53 clinical study, 56–57 non-toxicity against normal cells, 52 pharmacokinetics, 48 p53 influence, 51–52 properties antioxidant, 46 free radical scavenging activity, 47 interaction, enzyme systems, 47–48 nitric oxide inhibitory action, 47 xanthine oxidase inhibition, 47 source, 45 structure, 45–46 synergism, drugs, 53–56 R Radiation therapy, 126 Reactive oxygen species (ROS) Allium compounds, apoptosis, 175–176 BITC, 115 Brassica compounds, apoptosis, 181–182 malignant cells, allium compounds, 172 signaling, 75–77 RNA modulation, 22–24 S S-allylcysteine sulfoxide (SAC), 171 4ß,27-dihydroxy-1-oxo-5ß,6ßepoxywitha-2,24-dienolide See Withaferin A (WFA) Signaling pathways Allium compounds, apoptosis, 173f alteration in, phytochemicals application, 12–13 Brassica compounds, apoptosis, 179f Soy phytoestrogens classification, 195 clinical trials, 209, 210t epigenetic mechanisms, prostate cancer DNA methylation, 205–207 histone modifications, 207 miRNAs regulation, 207–209 metabolism, 195 molecular effects, 195–205 angiogenesis inhibition, 201–202 antioxidant activity, 203–205 apoptosis, 199–201 cell-cycle processes, 196–199 estrogenic activity, 195–196 metastasis inhibition, 202–203 Spindle assembly checkpoint (SAC), 79 STAT3 BITC, 115 signaling, 50–51 Structural–activity relationship (SAR), withanolides, 83 Sulforaphane (SFN), 178 See also Brassica angiogenesis, 120 cancer cells target, ITCs, 120–121 cell proliferation and growth, 120 with 5-fluorouracil, 125–126 metastasis, 121 mitochondrial cell death, 120–121 source, 120 toxicity studies, 121 in vivo studies, 121 Sulfur-containing compounds Allium vegetables (see Allium) cruciferous vegetables (see Brassica) glucosinolates, 177–178 Synergistic action, 84–86 T TNF-α, 51 Topoisomerases I/II, 14–15 Transcription factors, 79–81 262 Tryptanthrin angiogenesis, 64 anticancer properties, 58–62 cancer development prevention anti-inflammatory activity, 63–64 antioxidant activity, 63 chemistry, 57 cytotoxic properties, 58–62 medicinal value, 58 source, 57 structural modification, 62–63 toxicological analysis, 64 in vitro and in vivo, 60t Tumor growth and invasiveness, quercetin, 50–51 Tumor-inhibitory activity, 145–153 Subject Index W UPR, 24–25 Withaferin A (WFA) anticancer activity, 74–75, 82t apoptosis, 76–77 cytoskeletal-directed agents, 77–78 heat shock proteins, 81–84 metabolic enzymes, 84 mitosis inhibition, 79 NF-κB family, 79 proteasomal inhibition, 78–79 reactive oxygen species (ROS) signaling, 75–77 STAT3, 80 structure, 74–75, 74f synergistic action, 84–86 transcription factors, 79–81 Withania somnifera L Dunal (Solanaceae), 74 See also Withaferin A (WFA) Withanolides structure, 74–75, 74f World Health Organization (WHO), 168 V X Vimentin, 77–78 Xanthine oxidase inhibition, 47 U ... food science In this (Volume 37) and previous (Volume 36) volumes of The Enzymes, we attempted to compile studies on these topics and to discuss the mechanism of action of the phytochemicals in... Because of the considerable studies on the molecular mechanisms of many phytochemicals functions, and the extensive reviews presented by the experts in the volumes 36 and 37 of The Enzymes, we... mechanism of the anticancer effect of isoprenoids, polyphenols, and flavonoids was described in the previous volume In the current volume (Volume 37) , we continued and expanded the discussion