Potentiation of paclitaxel cytotoxicity by inostamycin in human small cell lung carcinoma, Ms-1 cells

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

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

In the present study, we found that inostamycin increased the ability of paclitaxel to induce apoptosis in Ms-1 cells. A considerably higher concentration of paclitaxel was required for the induction of apoptosis in Ms-1 cells than in other cell lines tested. Treatment of Ms-1 cells with inostamycin, an inhibitor of phosphatidylinositol (PI) synthesis, reduced the dosage of paclitaxel required to induce cell death by apoptosis. This effect of inostamycin is specific to Ms-1 cells, and inostamycin did not increase the cytotoxicity of other antitumor drugs such as adriamycin, vinblastine, methotrexate, cisplatin, etoposide, or camptothecin in Ms-1 cells. Addition of inostamycin to paclitaxel-treated cells caused a significant increase in the sub G1 peak, representing apoptosis, which was accompanied by a decrease in the G2/M peak seen in paclitaxel-treated Ms-1 cells, without affecting paclitaxel-inhibited tubulin depolymerization. Moreover, paclitaxel did not enhance inostamycin-inhibited PI synthesis. The expression levels of Bcl-2, Bax, and Bcl-X(L) were not changed following the co-treatment with inostamycin plus paclitaxel, whereas the activated form of caspase-3 was markedly increased. Thus, inostamycin is a chemosensitizer of paclitaxel in small cell lung carcinoma Ms-1 cells.

Original languageEnglish
Pages (from-to)970-976
Number of pages7
JournalJapanese Journal of Cancer Research
Volume89
Issue number9
DOIs
Publication statusPublished - 1998 Sep

Keywords

  • Apoptosis
  • Caspase-3
  • Inostamycin
  • Paclitaxel
  • Small cell lung carcinoma

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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