2-Methoxyestradiol induces G2/M arrest and apoptosis in prostate cancer

Laila R. Qadan, Carlos Perez-Stable, Curtis Anderson, Gianluca D'Ippolito, Alan Herron, Guy Howard, Bernard A. Roos

Research output: Contribution to journalArticle

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Abstract

Few therapeutic treatment options are available for patients suffering from metastatic androgen-independent prostate cancer. We investigated the ability of the estrogen metabolite 2-methoxyestradiol to inhibit the proliferation of a variety of human prostate cancer cell lines in vitro and to inhibit the growth of androgen-independent prostate cancer in a transgenic mouse model in vivo. Our results showed that 2-methoxyestradiol is a powerful growth inhibitor of LNCaP, DU 145, PC-3, and ALVA-31 prostate cancer cells. Cell flow cytometry of 2-methoxyestradiol-treated DU 145 cells showed a marked accumulation of cells in the G2/M phase of the cell cycle and an increase in the sub-G1 fraction (apoptotic). In addition, staining for annexin V, changes in nuclear morphology, and inhibition of caspase activity support a role for apoptosis. More importantly, we showed that 2-methoxyestradiol inhibits prostate tumor progression in the Gγ/T-15 transgenic mouse model of androgen-independent prostate cancer without toxic side effects. These results in cell culture and an animal model support investigations into the clinical use of 2-methoxyestradiol in patients with androgen-independent prostate cancer.

Original languageEnglish
Pages (from-to)1259-1266
Number of pages8
JournalBiochemical and Biophysical Research Communications
Volume285
Issue number5
DOIs
StatePublished - Oct 10 2001

Fingerprint

Prostatic Neoplasms
Androgens
Apoptosis
Cells
Transgenic Mice
Growth Inhibitors
Flow cytometry
Poisons
Annexin A5
Caspases
Metabolites
Cell culture
G2 Phase
Tumors
Estrogens
Animals
Cell Division
2-methoxyestradiol
Prostate
Cell Cycle

Keywords

  • Annexins
  • Estrogens
  • Flow cytometry
  • Necrosis
  • Transgenic mice

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

2-Methoxyestradiol induces G2/M arrest and apoptosis in prostate cancer. / Qadan, Laila R.; Perez-Stable, Carlos; Anderson, Curtis; D'Ippolito, Gianluca; Herron, Alan; Howard, Guy; Roos, Bernard A.

In: Biochemical and Biophysical Research Communications, Vol. 285, No. 5, 10.10.2001, p. 1259-1266.

Research output: Contribution to journalArticle

Qadan, Laila R. ; Perez-Stable, Carlos ; Anderson, Curtis ; D'Ippolito, Gianluca ; Herron, Alan ; Howard, Guy ; Roos, Bernard A. / 2-Methoxyestradiol induces G2/M arrest and apoptosis in prostate cancer. In: Biochemical and Biophysical Research Communications. 2001 ; Vol. 285, No. 5. pp. 1259-1266.
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