| Summary: | 碩士 === 中山醫學大學 === 生化暨生物科技研究所 === 99 === Flavonoids are a group of polyphenol compounds that exist extensively in dietary foods of vegetables and fruits, and the biological effects of flavonoids are anti-oxidant, anti-microbial, and anti-inflammatory activities. Recently, more and more studies have showed that flavonoids have the anti-tumor and anti-carcinogenesis effects. Therefore, the anti-tumor effects of flavanone （flavanone、2''-OH flavanone、3''-OH flavanone、4''-OH flavanone、5''-OH flavanone、6''-OH flavanone、7''-OH flavanone） in the osteosarcoma cell line （U-2 OS、143 B、MG-63、SaOS2） were analyzed. The result of MTT assay indicated that effect of flavanone、2''-OH flavanone and 3''-OH flavanone showed the most potent cytotoxic effect in the osteosarcoma cell line, and we also found that 2''-OH flavanoneare was the most potent cytotoxic compound. The result of cell’s live and death number calculation showed that 2''-OH flavanone induced the death number increasing of osteosarcoma cells. The further way, we found the phenomenon of chromatin condensation、mitochondria membrane potential change and diploid cell （sub-G1 phase） appearance after treatment to 143 B cell. Then, we analyzed the expression of apoptotic protein molecule by western blotting. The result showed the activation of caspase-3、caspase-8 and caspase-9. Therefore, the activation of caspase evidenced the occurrence of apoptosis. The result showed that 2''-OH flavanone increased the expression of TRAIL（TNF-released apoptosis-inducing ligand） and DR5 （Death receptor 5）. On the other hand, the result also showed that 2''-OH flavanone induced cytochrome c was released from mitochondria. We also found the anti-apoptotic proteins （Bcl-2、Bcl-xL）were inhibited, and the pro-apoptotic proteins（Bid、Bax、Bcl-xS）were activated. Therefore, the 2''-OH flavanone induced the 143 B cell apoptosis through TRAIL-DR5 pathway.Finally, we conducted the in vivo experiment（143 B-BALB/c nude mice）. The result showed that tumor growth were suppressed by 2''-OH flavanone. These results indicated that 2''-OH flavanone activated the extrinsic pathway and the intrinsic pathway through TRAIL-DR5 pathway, and it had potent effect to tumor growth in in vivo model. Therefore, 2''-hydroxyflavanone is a potent biological activity compound for the development of cancer chemotherapy.
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