Inhibition of aromatase activity and growth suppression by 4-methoxy-4-androstene-3,17-dione in an androgen sensitive human prostatic carcinoma cell line

Janice L. Block, Norman L. Block, Bal L. Lokeshwar

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Aromatization of testosterone to estradiol was investigated in a human prostatic carcinoma cell line, LNCaP. A saturable, dose and time-dependent aromatization of testosterone was observed. Kinetic parameters, K(m) (201 nM) and V(max) (0.76 pmol/h per mg) and also the inhibition constants (K(i)) for various aromatase inhibitors were calculated from standard Lineweaver-Burke plots. The steroidal aromatase inhibitor 4-hydroxy-4-androstene-3,17-dione (4-OHA) and its derivative, 4-methoxy-4-androstene-3,17-dione (4-OMA), inhibited aromatization of testosterone in a competitive pattern of inhibition. The derivative 4-OMA is the stronger inhibitor of the two, with an apparent K(i) of 1.12 μM, whereas the apparent K(i) of 4-OHA is 3.28 μM. Long term incubation with 4-OMA suppressed proliferative activity of LNCaP cells in the presence of physiological levels of testosterone (10-10 M to 10-7 M). In contrast, 4-OHA was a growth promoter. These results suggest a potential role for aromatase in hormone responsive prostate cancer.

Original languageEnglish (US)
Pages (from-to)143-148
Number of pages6
JournalCancer letters
Volume101
Issue number2
DOIs
StatePublished - Mar 29 1996

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Keywords

  • Androgens
  • Aromatase
  • Growth suppression
  • Prostate cancer

ASJC Scopus subject areas

  • Cancer Research
  • Molecular Biology
  • Oncology

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