A novel natural product GP-1 induces apoptosis in human hepatocellular carcinoma cells

• Main Authors: Yu-Hau Tzeng, 曾昱豪
• Other Authors: Shen-Jeu Won
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/57663070470584263195

碩士 === 國立成功大學 === 微生物及免疫學研究所 === 94 === Human hepatocellular carcinoma (HCC) is the fifth most frequent cancer and is the third most common cause of cancer-related death worldwide. Unfortunately, it does not response well to chemotherapy and has a poor prognosis of patients. The crude extract of the pericarp of Garcinia subelliptica (G. subelliptica) is a remedy commonly using to treat patients of aborigine in Taiwan. Previous studies have reported that constituents of the wood and root bark of G. subelliptica containing some compounds possess inhibitory activity against DNA topoisomerase, and the anti-inflammatory activity. Recent study has shown that a new benzoylphloroglucinol, garcinielliptone FB extracted from the pericarp of G. subelliptica exhibits cytotoxic activity against several tumor cells. The present study demonstrates that GP-1, a novel pure compound isolated from G. subelliptica, inhibited growth of HCC Hep-3B cells with the IC50 of 12.84 mM at day 6 of post-treatment. This inhibitory effect may be due to the process of apoptosis which was characterized by increase of sub-G1 DNA content and production of DNA fragments. The mechanism of apoptosis may be associated with the activation of caspase-2 and caspase-8, decrease cytosolic Bid, loss of mitochondrial membrane potential, release of cytochrome c and Smac/DIABLO to cytosol, decrease of XIAP, induction of caspase-9 and caspase-3, and elevation of nuclear DFF40. Moreover, AIF was released from mitochondria and entered to the nucleus in response to GP-1. These findings described the signaling pathway in GP-1 treated Hep-3B cells, and may provide a new sight of anti-cancer drug for clinical use.