Chemotherapeutic effect of tamoxifen on temozolomide-resistant gliomas.

Tamoxifen, a selective estrogen receptor modulator, is widely used in chemotherapy of estrogen receptor-positive breast cancer. Recent studies have indicated that tamoxifen might have potential chemotherapeutic effect on glioma. In the present study, we determined the chemotherapeutic action of tamoxifen on human glioma cell lines. Methylation of 06-methylguanine-DNA methyltransferase expression was identified in A172, U251 and BT325 glioma cell lines, but not U87 cell line. Consistently, A172, U251 and BT325 cell lines are resistant to temozolomide. Tamoxifen induced significant cytotoxic action in A172, U251, BT325, and U87 cell lines. Further Hoechst 33342 staining and apoptosis flow cytometric analysis demonstrated that tamoxifen induced apoptosis in BT325 cell line. Mitochondrial complex analysis indicated that tamoxifen, but not other estrogen receptor modulators, dose dependently inhibit complex I activity. In summary, our study suggests that tamoxifen might have chemotherapeutic effect on temozolomide resistant glioma through its direct action on mitochondrial complex I inhibition and could provide further evidence to support future clinical trial of tamoxifen for the treatment of glioblastoma.