Inhibition of cyclin D1 expression and induction of apoptosis by inostamycin in small cell lung carcinoma cells

Masaya Imoto, Keiko Tanabe, Siro Simizu, Etsu Tashiro, Minoru Takada, Kazuo Umezawa

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22 Citations (Scopus)


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 D, and increased cyclin-dependent kinase inhibitors such as p21(WAF1) and p27(KIP1) 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.

Original languageEnglish
Pages (from-to)315-322
Number of pages8
JournalJapanese Journal of Cancer Research
Issue number3
Publication statusPublished - 1998 Mar


  • Caspase-3
  • Cyclin D1
  • Inostomycin
  • p27(KIP1)

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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