Open AccessPotentiation of Paclitaxel Cytotoxicity by Inostamycin in Human Small Cell Lung Carcinoma, Ms‐1 Cells
Author(s) -
Simizu Siro,
Tanabe Keiko,
Tashiro Etsu,
Takada Minoru,
Umezawa Kazuo,
Imoto Masaya
Publication year - 1998
Publication title -
japanese journal of cancer research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 0910-5050
DOI - 10.1111/j.1349-7006.1998.tb00656.x
Subject(s) - paclitaxel , cytotoxicity , apoptosis , vinblastine , camptothecin , chemosensitizer , etoposide , pharmacology , cisplatin , carmustine , chemistry , chemotherapy , cancer research , medicine , in vitro , biochemistry
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.