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KMID : 1140120120170010045
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Cancer Prevention Research
2012 Volume.17 No. 1 p.45 ~ p.55
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PI3K/Akt/mTOR Mediated Anti-proliferation by the Extract of Fungus Chaetomium sp. in SK-Hep1 Human Hepatocellular Carcinoma Cells
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Abstract
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The marine environment has immeasurable diversity of the chemical and the biological compounds and is an extraordinary resource for the discovery of new anti-cancer drugs. In this study, we investigated the anti-cancer effect of the extract of marine algae-derived symbiotic fungus Chaetomium sp. on SK-Hep1 human hepatocellular carcinoma cells. The extract exhibited inhibition of cell proliferation by inducing apoptosis, cell cycle arrest at G1/S phase and autophagic cell death. The results showed that apoptosis resulted from the activation of pro-apoptotic proteins (tBid, Bad, PUMA) and caspases (-3 and -8). We identified that the extract arrested cell cycle at sub-G1 phase and increased expression of p21CIP1/WAF1 while reduced expression of cdc25A and E2F-1. The extract also inhibited the activation of PI3K regulatory subunit (PI3K p110α) and downstream targets such as Akt, mTOR and p70S6K. The cells treated with the extract finally showed autophagy by the up-regulation of Atg5, 7, 12 and LC3B. The results suggested that the extract of fungus Chaetomium sp. has a potential anti-cancer effect on SK-Hep1 cells.
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KEYWORD
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Chaetomium sp., Apoptosis, Cell cycle arrest, PI3K/Akt/mTOR pathway, Autophagy,
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