Mohanty Suchismita, Adhikary Arghya, Chakrabarty Samik, Sa Gaurisankar, Das Tanya
Division of Molecular Medicine, Bose Institute, P1/12 CIT Scheme VIIM, Kolkata, India.
Front Biosci (Schol Ed). 2012 Jan 1;4(1):300-20. doi: 10.2741/270.
With phytochemicals executing a plethora of anti-tumor mechanisms, targeting the 'guardian angel' p53 appears to be a critical strategy to energize the process of cancer therapeutics. Regulation of anti-tumor p53 functions by dietary plant polyphenols particularly black tea and its active component theaflavins has gained immense recognition from the point of view of both efficacy and safety. This review highlights the complexities of p53 functions, molecular mechanisms of its inactivation in cancer, and therapeutic strategies for rescuing p53 dysfunction in tumors using theaflavins. It describes how theaflavins, by steering a single molecular target - p53, regulate multiple hallmarks of carcinogenesis i.e., tumor glycolysis, angiogenesis, metastasis, apoptosis and drug resistance. Additionally, considering the rising of the current concept of cancer stem cells (CSCs), the sole participant in tumor evolution, the review discusses about the possible role of theaflavin-p53 cross talk in targeting CSCs. Such attempts to target the complexities of p53 functions during neogenesis will be of immense help in developing a "new" strategy for successful cancer prevention and therapy by theaflavins.
由于植物化学物质具有多种抗肿瘤机制,靶向“守护天使”p53似乎是推动癌症治疗进程的关键策略。从疗效和安全性的角度来看,膳食植物多酚尤其是红茶及其活性成分茶黄素对抗肿瘤p53功能的调节已获得广泛认可。本综述重点介绍了p53功能的复杂性、其在癌症中失活的分子机制,以及使用茶黄素挽救肿瘤中p53功能障碍的治疗策略。它描述了茶黄素如何通过调控单一分子靶点——p53,调节致癌作用的多个标志,即肿瘤糖酵解、血管生成、转移、凋亡和耐药性。此外,鉴于当前癌症干细胞(CSCs)这一肿瘤演变的唯一参与者概念的兴起,本综述讨论了茶黄素-p53相互作用在靶向CSCs方面的可能作用。这种针对新生过程中p53功能复杂性的靶向尝试,将对开发通过茶黄素成功预防和治疗癌症的“新”策略有极大帮助。