Grifolin, a potential antitumor natural product from the mushroom Albatrellus confluens, inhibits tumor cell growth by inducing apoptosis in vitro |
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Authors: | Ye Mao Liu Ji-Kai Lu Zhong-Xin Zhao Yan Liu Su-Fang Li Li-Li Tan Ming Weng Xin-Xian Li Wei Cao Ya |
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Affiliation: | Cancer Research Institute, Xiangya School of Medicine, Central South University, Changsha, Hunan 410078, PR China. |
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Abstract: | Grifolin is a natural biologically active substance isolated from the fresh fruiting bodies of the mushroom Albatrellus confluens. Here, for the first time, we describe a novel activity of grifolin, namely its ability to inhibit the growth of tumor cells by the induction of apoptosis. Grifolin strongly inhibited the growth of tumor cell lines: CNE1, HeLa, MCF7, SW480, K562, Raji and B95-8. Analysis of acridine orange (AO)/ethidium bromide (EB) staining and flow cytometry showed that grifolin possessed apoptosis induction activity to CNE1, HeLa, MCF7 and SW480. Furthermore, the cytochrome c release from mitochondria was detected by confocal microscopy in CNE1 cells after a 12h treatment with grifolin. The increase of caspase-8, 9, 3 activities revealed that caspase was a key mediator of the apoptotic pathway induced by grifolin, and the underexpression of Bcl-2 and up-regulation of Bax resulted in the increase of Bax: Bcl-2 ratio, suggesting that Bcl-2 family involved in the control of apoptosis. Owing to the combination of the significant antitumor activity by inducing apoptosis and natural abundance of the compound, grifolin holds the promise of being an interesting antitumor agent that deserves further laboratory and in vivo exploration. |
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Keywords: | IC50, 50% inhibitory concentration DMSO, dimethyl sulfoxide MTT, 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide PBS, phosphate-buffered saline AO, acridine orange EB, ethidium bromide PI, propidium iodide IETD-pNA, Ile-Glu-Thr-Asp conjugated to p-nitroanilide LEHD-pNA, Leu-Glu-His-Asp conjugated to p-nitroanilide DEVD-pNA, Asp-Glu-Val-Asp conjugated to p-nitroanilide |
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