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KMID : 1140120100150020172
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Cancer Prevention Research
2010 Volume.15 No. 2 p.172 ~ p.177
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Inhibition of Telomerase Activity by Proteoglycan of Phellinus linteus in U937 Human Leukemia Cells
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Hong Su-Hyun
Han Min-Ho
Kim Hye-Jeong
Choi Yung-Hyun
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Abstract
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Recent studies demonstrated that proteoglycan extracted from Phellinus linteus has a potent anti-tumor and/or anti-inflammatory activity by leading to induction of apoptosis and inhibition of prostaglandin E2 production; however, its mechanism of action and its molecular targets on the telomere length regulation in human cancer remain unclear. In this study, we investigated the effect of proteoglycan on the levels of telomere regulatory components and the activity of telomerase in human leukemia U937 cells. Exposure of U937 cells to proteoglycan resulted in growth inhibition and induction of apoptosis as measured by MTT assay and flow cytometry analysis, which was associated with induction of tumor suppressor p53 and cyclin-dependent kinase inhibitor p21 (WAF1/CIP1). Proteoglycan treatment markedly inhibited the activity of telomerase, and the levels of and transcription factor c-myc, human telomerase reverse transcriptase (hTERT) and telomerase-associated protein-1 (TEP-1), main determinants of the telomerase enzymatic activity, were progressively down-regulated by proteoglycan treatment in a dose-dependent fashion. Taken together, these findings provide important new insights into the possible molecular mechanisms of the anti-cancer activity of proteoglycan.
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KEYWORD
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Phellinus linteus, Proteoglycan, Telomerase
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