Эпигаллокатехин и рак
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CONCLUSIONGTCs are promising agents for the chemoprevention of prostate cancer in the clinical setting (68,70–72,190). GTCs are most effective against early stage prostate carcinogenesis in laboratory (106,108,127) and clinical studies (70,71), and are attractive chemopreventive agents because of low toxicity (24,43–47) and specificity to transformed and malignant cells (48–52). The use of GTCs for prostate cancer chemoprevention is not without challenges. In vitro (Table 4) and in vivo (7) dosages have varied greatly by study and are not easily translated to clinical studies. Additionally, studies indicate that caution should be used when supplementing with high concentrations of GTCs because of unintended responses (187,188) and inhibitory actions on other compounds (57). Despite these challenges, several clinical trials have been carried out with GTCs (Table 5). Cell culture and animal models suggest that GTCs exert chemopreventive action against prostate cancer cells by targeting mechanisms essential to cancer cell growth, progression, and metastasis (7,38,172,181,182,189). We propose a novel model in which GTCs, particularly EGCG, exert chemopreventive effects on prostate cancer through 6 major mechanisms that work simultaneously and dependently, largely driven through proteasome inhibition induced regulation of the NFκB pathway. GTCs cause proteasome inhibition and subsequent cell cycle arrest, growth suppression, and ultimately apoptosis in prostate cancer cells and tissues. GTC-induced apoptosis results in the reduction of cancer cell dissemination, causing the inhibition of prostate cancer development, progression, and metastasis (Fig. 1). The six primary mechanisms of GTC-induced chemopreventive action on prostate cancer cells are seen consistently across laboratory and clinical studies. The pathways by which these mechanisms are regulated and activated do, however, vary by cell type and context, which is to be expected in the multifaceted processes pertaining to cell homeostasis and carcinogenesis. Understanding the anticarcinogenic activities and mechanisms of GTCs is essential to developing appropriate therapeutic modalities for the prevention of prostate cancer. Although GTCs act through distinct cell cycle and apoptotic pathways, the cumulative chemopreventative effect appears to be attributed to their well-coordinated ensemble rather than a single pathway (89,172,178). More studies are needed to gain insight into GTC-induced mechanisms of prostate cancer prevention and develop the most appropriate clinical settings in which to use green tea for chemoprevention (27,180). Research focused on the onco-genes, transcription factors, growth factors, cell cycle regulatory, and other factors affected by GTCs will inform these mechanistic studies (180). Efforts should continue to fill the lack of data that makes it difficult to extrapolate results from in vitro to in vivo to clinical studies (19,27,64,191). Bridging this gap will require more in vitro studies to confirm the mechanisms mentioned in this review and to identify new mechanisms and potential biomarkers of GTC chemoprevention in prostate cancer cells and tissues. Because of the context-specific differences inherent in biological systems, it critical that these mechanisms are tested in a variety of prostate cancer cell lines that differ by origin, hormone status, aggressiveness, and other factors. Only then can these mechanisms be tested in vivo with rodent models, validated in human phase II and phase III clinical studies, and appropriately applied to chemoprevention therapies (40). Additionally, transitioning from the use of individual GTCs, to purified GTC preparations, such as Polyphenon E, may provide a standardized compound that may more accurately reflect human tea consumption, deliver the maximum amount of GTCs without caffeine side effects, and provide more insight to GTC-induced chemopreventive mechanisms. Our laboratory studies are currently focusing on testing and refining the cumulative model of GTC chemoprevention in prostate cancer cells as a first step to fully elucidate the complex mechanism of GTC chemoprevention of prostate cancer in its entirety. Эпигенетические диеты: воздействие на эпигенома и рака. Ряд биологически активных пищевых компонентов представляют особый интерес в области эпигенетики. Многие из этих соединений дисплей противораковыми свойствами и может играть роль в рак профилактики. Многочисленные исследования показывают, что количество питательных соединений имеют эпигенетические цели в рак ячеек. Главное, возникающих доказательства наводят на мысль, что потребление диетических агенты могут изменять нормальное эпигенетических состояний, а также обратный аномальный ген активации или отключения звука. Эпигенетические модификации, индуцированных биологически активных пищевых соединений, которые, как полагают, чтобы быть полезным. Существенных доказательств монтажа, заявляя, что принято употреблять биологически активные пищевые факторы могут служить основанием для изменения эпигенома и могут быть включены в " эпигенетический диета". Биологически активные питательные компоненты эпигенетические диеты могут быть включены в регулярный режим питания и используется в лечебных целях в лечебных или химические целей. В данной статье в первую очередь будут ориентированы на пищевые факторы, которые продемонстрировали влияние эпигенома и которые могут быть использованы в сочетании с другими рак - профилактика и химиотерапевтических методов лечения. Epigenomics. 2011 Aug;3(4):503-18. doi: 10.2217/epi.11.71. жүктеу/скачать 1.88 Mb. Достарыңызбен бөлісу:
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