Absorption study showed that gossypetin was methoxylated and conjugated to form glucuronide during the first-pass metabolism after oral administration. Glucuronide conjugate was the major circulating form in the plasma. As determined by HPLC analysis, the total gossypetin concentration in the plasma was higher than the unchanged gossypetin indicating that most of gossypetin underwent first-pass metabolism. Moreover, urinary excretion was not a main elimination route. / Uses of foods and dietary supplements present a safe chemopreventive strategy. The application of phytochemicals for cancer prevention currently receives a great deal of attention. Flavonoids are known to be antiproliferative and may play an important role in the prevention of carcinogenesis. In addition to epidemiologic studies, basic science research to elucidate mechanisms and evaluate chemopreventive potential of phytochemicals is also necessary. In this study, gossypetin was found to have stronger antiproliferative activity when compared with quercetin, a well studied flavonoid, in human hepatocellular carcinoma (HepG2) cells and human breast carcinoma (MCF-7) cells. The results demonstrated that gossypetin induced growth inhibition in MCF-7 cell line by arresting cell cycle at G0/G1 phase. The inhibition of cell cycle progression was associated with the decrement of cyclin D1 expression, cdk6 kinase activity and phosphorylation of retinoblastoma protein (pRb). Although the cdk inhibitor p21 could not be detected, its upstream protein, p53 tumor suppressor protein, was activated by gossypetin in the MCF-7 cell line. Also, the proliferation of MCF-7 cells was suppressed through down-regulating the Erk1/2 pathway. / Ngai Lei-ka. / "August 2005." / Source: Dissertation Abstracts International, Volume: 67-11, Section: B, page: 6156. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2005. / Includes bibliographical references (p. 222-250). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Chan Wai-Lung, William. / Thesis submitted in: December 2000. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2001. / Includes bibliographical references (leaves 124-131). / Abstracts in English and Chinese. / Abstract --- p.i / Abstract (Chinese Version) --- p.iii / Acknowledgements --- p.v / Table of Contents --- p.vi / List of Tables --- p.ix / List of Figures --- p.xii / List of Abbreviations --- p.xvi / Chapter 1 --- Introduction --- p.1 / Literature Review --- p.4 / Chapter 1.1 --- A Brief Introduction of Cancer --- p.4 / Chapter 1.2 --- Natural Products as a Drug --- p.5 / Chapter 1.2.1 --- Development of terrestrial plants as a drug --- p.6 / Chapter 1.2.1.1 --- Anticancer drugs from terrestrial plants and Chinese medicinal herbs --- p.7 / Chapter 1.2.2 --- Development of marine organisms as a drug --- p.8 / Chapter 1.2.2.1 --- Anticancer drugs from marine organisms --- p.9 / Chapter 1.3 --- Anticlastogenic Study - an Anticancer Study --- p.10 / Chapter 1.3.1 --- Anticlastogenesis mechanisms study --- p.11 / Chapter 1.3.2 --- In vivo anticlastogenic study --- p.13 / Chapter 1.4 --- Anticlastogenic Study of Chinese Medicinal Herbs and Marine Algae --- p.17 / Chapter 1.4.1 --- Selection of nine Chinese medicinal herbs and three marine algae for anticlastogenic screening --- p.18 / Chapter 1.5 --- Methods of Investigation --- p.20 / Chapter 1.5.1 --- Extraction methods --- p.20 / Chapter 1.5.2 --- Single cell gel electrophoresis (Comet assay) --- p.21 / Chapter 2 --- Materials and Methods --- p.27 / Chapter 2.1 --- Materials --- p.27 / Chapter 2.1.1 --- Chinese medicinal herbs --- p.27 / Chapter 2.1.2 --- Marine algae --- p.27 / Chapter 2.1.3 --- Animals --- p.27 / Chapter 2.1.4 --- Chemicals and solutions --- p.28 / Chapter 2.2 --- Methods --- p.31 / Chapter 2.2.1 --- Crude extraction of natural products --- p.31 / Chapter 2.2.1.1 --- Water extraction of Chinese herbs --- p.31 / Chapter 2.2.1.2 --- Water extraction of marine algae --- p.31 / Chapter 2.2.2 --- Test for the effective dosage of clastogen ethyl methanesulfonate (EMS) to BALB/c mice --- p.31 / Chapter 2.2.2.1 --- In vitro test --- p.32 / Chapter 2.2.2.2 --- In vivo test --- p.32 / Chapter 2.2.3 --- Anticlastogenic bioassays --- p.33 / Chapter 2.2.3.1 --- In vitro anticlastogenic screening --- p.33 / Chapter 2.2.3.2 --- In vitro anticlastogenic mechanisms investigation --- p.33 / Chapter 2.2.3.3 --- In vivo anticlastogenic screening --- p.34 / Chapter 2.2.3.4 --- Different in vivo anticlastogenic treatment schedules --- p.35 / Chapter 2.2.4 --- Single cell gel electrophoresis assay (Comet assay) --- p.36 / Chapter 2.2.5 --- White blood cell viability determination --- p.37 / Chapter 2.2.6 --- Statistical analysis --- p.38 / Chapter 3 --- Results --- p.40 / Chapter 3.1 --- Extraction amount of different natural products and cell viability checking --- p.40 / Chapter 3.1.1 --- Chinese medicinal herbs --- p.40 / Chapter 3.1.2 --- Seaweeds --- p.40 / Chapter 3.1.3 --- Cell viability --- p.42 / Chapter 3.2 --- Effective dosage of clastogen EMS to BALB/c mice peripheral white blood cells --- p.42 / Chapter 3.2.1 --- In vitro --- p.42 / Chapter 3.2.2 --- In vivo --- p.42 / Chapter 3.3 --- In vitro anticlastogenic screen test and mechanisms investigation --- p.44 / Chapter 3.3.1 --- In vitro anticlastogenic screen test --- p.44 / Chapter 3.3.1.1 --- Chinese herbs --- p.44 / Chapter 3.3.1.2 --- Seaweeds --- p.53 / Chapter 3.3.2 --- In vitro anticlastogenic mechanisms investigation --- p.55 / Chapter 3.3.2.1 --- H. dilatata --- p.56 / Chapter 3.3.2.2 --- S. angustifolium --- p.56 / Chapter 3.3.2.3 --- S. siliquastrum --- p.63 / Chapter 3.4 --- In vivo anticlastogenic screen test and mechanisms investigation --- p.66 / Chapter 3.4.1 --- In vivo anticlastogenic screen test --- p.66 / Chapter 3.4.1.1 --- Chinese herbs --- p.66 / Chapter 3.4.1.2 --- Seaweeds --- p.73 / Chapter 3.4.2 --- Different treatment methods in in vivo anticlastogenic test --- p.86 / Chapter 3.4.2.1 --- Simultaneous application method --- p.86 / Chapter 3.4.2.2 --- Pre-drug treatment method --- p.91 / Chapter 3.4.2.3 --- Post drug treatment method --- p.91 / Chapter 4 --- Discussion --- p.94 / Chapter 4.1 --- Cell viability and water extracts in Chinese medicinal herbs and marine algae --- p.94 / Chapter 4.2 --- Clastogenic effect of EMS to pWBCs of BALB/c mice --- p.94 / Chapter 4.3 --- In vitro anticlastogenic screen test of nine water extracts of Chinese medicinal herbs and three water extracts of marine algae --- p.99 / Chapter 4.4 --- In vitro anticlastogenic mechanisms investigation of three \03 marine algae extracts --- p.103 / Chapter 4.5 --- In vivo anticlastogenic screen test of Chinese herbs extracts and seaweeds extracts --- p.108 / Chapter 4.6 --- Different administration methods in in vivo anticlastogenic test --- p.115 / Chapter 4.6.1 --- Intraperitoneal route of administration --- p.115 / Chapter 4.6.2 --- In vivo pre- and post-treatment methods --- p.116 / Chapter 5 --- Summary and Conclusion --- p.120 / References --- p.124

Cancer chemoprevention uses noncytotoxic drugs or nutrients to prevent, retard, or delay carcinogenesis. The future of cancer chemoprevention depends on understanding key cellular growth and proliferation-controlling events, developing markers of molecular carcinogenesis, surrogate endpoint biomarkers, and targeted chemopreventive approaches.

This review summarizes the principles of cancer chemoprevention and discusses the evidence from epidemiologic and experimental studies and preclinical and clinical trials of potential colorectal chemopreventive agents. The putative mechanisms of action of the drugs in chemoprevention and their potential to reduce the incidence and mortality rate of colorectal neoplasms are discussed. The future of colorectal chemoprevention will depend on important new insights into molecular carcinogenesis of colorectal cancer, application of molecular markers as surrogate endpoints, and ultimately on therapeutic targets of prevention in clinical trials.

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