Inhibition of cyclin D1 expression and induction of apoptosis by inostamycin in small cell lung carcinoma cells.
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| Abstract |
Previously, we demonstrated that inostamycin, an inhibitor of phosphatidylinositol turnover, caused cell cycle arrest at the G1 phase, inhibiting the expression of cyclins D1 and E in normal cells. In the present study, we examined the effects of inostamycin on cell cycle progression and apoptosis in human small cell lung carcinoma Ms-1 cells. Treatment of exponentially proliferating Ms-1 cells with low concentrations of inostamycin caused cells to accumulate in the G1 phase. We found that inostamycin decreased cyclin D1, and increased cyclin-dependent kinase inhibitors such as p21WAF1 and p27KIP1 in Ms-1 cells. On the other hand, higher concentrations of inostamycin induced morphological apoptosis and DNA fragmentation in Ms-1 cells without affecting the expression of p53, Bcl-2 and Bax. Inostamycin-induced apoptosis was suppressed by an inhibitor of caspase-3, and a 17 kDa fragment of activated caspase-3 was detected following inostamycin treatment. Therefore, caspase-3(-like) would appear to be involved in inostamycin-induced apoptosis. On the other hand, an inhibitor of caspase-3(-like) proteases did not affect the inhibitory effect of inostamycin on cyclin D1 expression, suggesting that caspase-3(-like) proteases were not responsible for inostamycin-induced G1 arrest.
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| Authors | M Imoto, K Tanabe, S Simizu, E Tashiro, M Takada, K Umezawa |
| Journal | Japanese journal of cancer research : Gann (Jpn J Cancer Res) Vol. 89 Issue 3 Pg. 315-22 (Mar 1998) ISSN: 0910-5050 [Print] Japan |
| PMID | 9600126 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't) |
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