title: Chemotherapeutic effect of tamoxifen on temozolomide-resistant gliomas.
abstract: Tamoxifen, a selective estrogen receptor modulator, is widely used in the chemotherapy of estrogen receptor-positive breast cancer. Recent studies have indicated that tamoxifen might have a 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 was identified in A172, U251, and BT325 glioma cell lines, but not in the 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 the BT325 cell line. Mitochondrial complex analysis indicated that tamoxifen, but not other estrogen receptor modulators, dose-dependently inhibits complex I activity. In summary, our study suggests that tamoxifen might have a chemotherapeutic effect on temozolomide-resistant glioma through its direct action on mitochondrial complex I inhibition and could provide further evidence to support future clinical trials of tamoxifen for the treatment of glioblastoma.
authors.affiliation: aDepartment of Pathophysiology, Beijing Neurosurgical Institute bCenter of Brain Tumor, Beijing Institute for Brain Disorders cBeijing Key Laboratory of Brian Tumor, Beijing Neurosurgical Institute, Beijing Tiantan Hospital dDepartment of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing eDepartment of Neurology, Second Hospital of Hebei Medical University, Shijiazhuang, China fDepartment of Pharmacology and Neuroscience, University of North Texas Health Science Center, Fort Worth, Texas, USA.
authors.forename: Weiliang
authors.initials: W
authors.lastname: He
authors.forename: Ran
authors.initials: R
authors.lastname: Liu
authors.forename: Shao-Hua
authors.initials: SH
authors.lastname: Yang
authors.forename: Fang
authors.initials: F
authors.lastname: Yuan
mesh_terms: D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D015254:DNA Modification Methylases / Q000235:genetics / Q000378:metabolism; D045643:DNA Repair Enzymes / Q000235:genetics / Q000378:metabolism; D003606:Dacarbazine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D042967:Electron Transport Complex I / Q000037:antagonists & inhibitors; D005910:Glioma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D008297:Male; D008745:Methylation; D008928:Mitochondria / Q000378:metabolism; D011401:Promoter Regions, Genetic; D017207:Rats, Sprague-Dawley; D013629:Tamoxifen / Q000494:pharmacology*; D000077204:Temozolomide; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D025521:Tumor Suppressor Proteins; D013629:Tamoxifen; D003606:Dacarbazine; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes; D042967:Electron Transport Complex I; D000077204:Temozolomide