Cell cycle block and apoptosis induction in a human melanoma cell line following treatment with 2-methoxyoestradiol: Therapeutic implications?

Rita Ghosh, Ann M. Ott, Divya Seetharam, Thomas J. Slaga, Addanki P. Kumar

Research output: Contribution to journalArticle

33 Scopus citations

Abstract

Due to minimal success with non-surgical treatment options for melanoma, it is imperative that other compounds be tested for potential preventive/therapeutic use. We have tested the ability of the endogenous oestrogenic metabolite 2-methoxyestradiol (2-ME) to inhibit the growth of human melanoma cells in culture. 2-ME inhibited the growth of all the melanoma cells tested, without inhibiting the growth of non-tumorigenic cells. Microscopic observations showed that treated cells exhibit the characteristic features of apoptosis. Examination of the molecular mechanism in WM98-1 cells, using biochemical assays such as a modified TUNEL staining and DNA fragmentation, confirmed the induction of apoptosis following 2-ME treatment. Flow cytometry analysis showed that, following treatment, cells are arrested in the G2/M phase of the cell cycle. Western blot analysis of the G2/M regulatory proteins suggests that cdc2 is involved in the cell cycle block by Myt1 phosphorylation following 2-ME treatment. Furthermore, examination of the levels of apoptosis regulatory proteins showed that, while levels of p53, Bax and p21 are higher, that of anti-apoptotic Bcl-2 is undetectable in cells treated with 2-ME compared with untreated controls. Taken together these results have major implications for the use of 2-ME for melanoma management. Melanoma Res 13:119-127

Original languageEnglish (US)
Pages (from-to)119-127
Number of pages9
JournalMelanoma Research
Volume13
Issue number2
DOIs
StatePublished - Apr 1 2003
Externally publishedYes

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Keywords

  • 2-methoxyoestradiol
  • Apoptosis
  • Cell cycle
  • Melanoma
  • Proliferation

ASJC Scopus subject areas

  • Oncology
  • Dermatology
  • Cancer Research

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