Antitumor Activity Of Curcumin Analogs And The Possible Mechanism

Cancer has been a serious threat to human health.Chemical treatment is still one of the major tools for cancer therapy.The natural product-based screening and the active natural compound-based structure modification(for improving chemical and physical properties,enhancing anti-tumor effects and reducing toxicities) have been increasingly believed to be good approaches to provide a base for lead identification and new drug development.In this thesis,the MTT assay was used to evaluate the cytotoxicity of a series of natural compounds and pariticularly curcumin structural analogs against several cancer cell lines including C6,HepG2,Bel-7402 and SMMC-7721 tumor cells.The results showed that two curcumin analogs out of others,ccm-5 and ccm-14,exhibited the highest cytotoxic activities in these tumor cells.The flow cytometry with AnnexinV-EGFP/PI apoptosis detection kit and PI staining were also used to investigate the effects of ccm-5 and ccm-14 on SMMC-7721 apoptosis and cell cycle distribution.The signaling possibly involved in the compound-triggered apoptosis of the cancer cells was then evaluated by Western-Blot analysis of caspase-3.The expression of the protein in the cells with the treatment of ccm-5 or ccm-14 was up-regulated in a dose-dependent manner,suggesting that the anti-tumor activities of these curcumin analogs might be related with caspase-3 cascade.