Chemotherapeutic effect of tamoxifen on temozolomide-resistant gliomas

Weiliang He, Ran Liu, Shaohua Yang, Fang Yuan

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)293-300
Number of pages8
JournalAnti-Cancer Drugs
Volume26
Issue number3
DOIs
StatePublished - 1 Jan 2015

Fingerprint

temozolomide
Tamoxifen
Glioma
Cell Line
Apoptosis
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Methyltransferases
Glioblastoma
Estrogen Receptors
Methylation

Keywords

  • glioma
  • mitochondria
  • tamoxifen
  • temozolomide

Cite this

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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.",
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Chemotherapeutic effect of tamoxifen on temozolomide-resistant gliomas. / He, Weiliang; Liu, Ran; Yang, Shaohua; Yuan, Fang.

In: Anti-Cancer Drugs, Vol. 26, No. 3, 01.01.2015, p. 293-300.

Research output: Contribution to journalArticleResearchpeer-review

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