| Summary: | 碩士 === 國立成功大學 === 微生物及免疫學研究所 === 92 === Ch’an Su, a traditional Chinese medicine, has been used in cancer therapy in south area of China for hundreds of years. The antitumor mechanism of Chan Su is still unclear. Human hepatocellular carcinoma (HCC) is one of the most common malignant neoplasms in Taiwan with poor response to chemotherapy. Bufotalin is one of major constituents of Chan Su. In the present study, we are the first to explore the antitumor mechanism of bufotalin in HCC. The inhibition concentrations (IC50) of bufotalin on HCC Hep 3B cell growth was 0.24 mM at day 6 of post-treatment. At day 14 post-treatment, the IC50 of colony formation in soft agar was 0.12 mM. Bufotalin inhibited the growth of Hep 3B cells via apoptosis, following by phosphatidylserine exposure, increased in sub-G1 content, and DNA fragmentation. The molecular basis of bufotalin triggered apoptosis seems to associate with the activation of caspase-8, the loss of mitochondrial membrane potential, decreased the expression of XIAP, up expressions of mitochondrial tBid and Bak, and down expressions of mitochondrial Bcl-2 and Bcl-XL, than activation of caspase-9 and -3, which, in turn, increased nuclear cleavages of poly (ADP-ribose) polymerase and DFF45, and DNA fragmentation. These findings indicate that bufotalin is an anticancer agent that triggered apoptosis via the activation of caspase-8.
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