Anticancer effects of 10-hydroxycamptothecin induce apoptosis of human osteosarcoma through activating caspase-3, p53 and cytochrome c pathways

10-羟基喜树碱的抗癌作用通过激活 caspase-3、p53 和细胞色素 c 通路诱导人骨肉瘤细胞凋亡

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作者:Xiong Min, Han Heng, Hua-Long Yu, Mao Dan, Chen Jie, Yun Zeng, He Ning, Zhi-Gang Liu, Zhi-Yong Wang, Wang Lin

Abstract

In order to evaluate the anticancer effect of 10-hydroxycamptothecin (HCPT) in terms of inducing the apoptosis of human osteosarcoma cells, its apoptosis-inducing molecular mechanisms were investigated. In the present study, the anticancer effects of HCPT were revealed to result in suppressed cell viability, increased cytotoxicity, the induction of apoptosis and an augmented apoptotic nucleolus of human osteosarcoma cells. MG-63 cells were cultured with HCPT (0, 20, 40 and 80 nM) for 24 and 48 h. An MTT assay and a lactate dehydrogenase assay were used to analyze the anticancer effect of HCPT on cell viability and cytotoxicity in MG-63 cells. MG-63 cell apoptosis, and caspase-9 and caspase-3 activity levels were evaluated using flow cytometry and an ELISA. Western blot analysis was used to detect the protein expression levels of p53, poly (ADP-ribose) polymerase-1 (PARP-1), cytochrome c and B cell lymphoma-2 (Bcl-2) in MG-63 cells. The anticancer effects of HCPT were demonstrated to significantly activate the protein expression of p53, PARP-1 and cytochrome c, and suppress Bcl-2 protein expression and promote the activity of caspase-9 and caspase-3 in human osteosarcoma cells. In conclusion, the anticancer effects of HCPT appear to induce the apoptosis of human osteosarcoma cells through the activation of the caspase-3, p53 and cytochrome c pathways.

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