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Japanese Journal of Cancer Research : Gann logoLink to Japanese Journal of Cancer Research : Gann
. 1998 Sep;89(9):970–976. doi: 10.1111/j.1349-7006.1998.tb00656.x

Potentiation of Paclitaxel Cytotoxicity by Inostamycin in Human Small Cell Lung Carcinoma, Ms‐1 Cells

Siro Simizu 1, Keiko Tanabe 1, Etsu Tashiro 1, Minoru Takada 2, Kazuo Umezawa 1, Masaya Imoto 1,✉
PMCID: PMC5921940  PMID: 9818034

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‐XL 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.

Keywords: key words, Paclitaxel, Apoptosis, Small cell lung carcinoma, Inostamycin, Caspase‐3

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This work was partly supported by grants from the Ministry of Education, Science, Sports and Culture of Japan.

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