GROWTH-INHIBITION OF T47D HUMAN BREAST-CANCER CELLS BY THE NEW ANTIAROMATASE STEROID 3-METHYLENE-1,4-ANDROSTADIEN-17-ONE

  • Authors:
    • F GIROUARD
    • L TAN
  • View Affiliations

  • Published online on: November 1, 1993     https://doi.org/10.3892/ijo.3.5.891
  • Pages: 891-896
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Abstract

The C19 steroid, 3-methylene-1,4-androstadien-17-one (3-methylene-1-dehydro-4-androsten-17-one, abbrev. 3MDA) was synthesized by microbial dehydrogenation with Arthrobacter simplex from the corresponding 1,2-saturated, 3-methylene-4-androsten-17-one. The new steroid induces a Type-1 optical difference spectrum with Cytochrome P450 aromatase from human placentae (K(s) 1.61 muM). Kinetic inhibition studies with placental microsomes show: (i) 3MDA inhibits aromatase irreversibly (k(inact) 0.026 min-1), (ii) the inhibition is time- and concentration-dependent, (iii) it follows pseudo first-order kinetics, and (iv) the inhibition requires the presence of the cofactor NADPH. Human T47D breast tumor cells are able to transform C-14-labeled androstenedione into radioactive estrone/estradiol, as we have established by repetitive HPLC purifications. We have thus clearly demonstrated the presence of an endogenous steroidal androgen-aromatizing enzyme in these breast tumor cells. Besides inhibiting human placental aromatase activity, 3MDA at concentrations of 5-20 muM also significantly decreases the growth of cultured T47D cells as measured by the incorporation of [H-3]thymidine into DNA, but without causing cell death due to cytotoxicity. These findings prompt us to propose 3MDA as a new, mechanism-based suicide substrate of the human aromatase enzyme with potential utility as a 'second generation' anti-breast cancer agent.

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November 1993
Volume 3 Issue 5

Print ISSN: 1019-6439
Online ISSN:1791-2423

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Spandidos Publications style
GIROUARD F and GIROUARD F: GROWTH-INHIBITION OF T47D HUMAN BREAST-CANCER CELLS BY THE NEW ANTIAROMATASE STEROID 3-METHYLENE-1,4-ANDROSTADIEN-17-ONE. Int J Oncol 3: 891-896, 1993
APA
GIROUARD, F., & GIROUARD, F. (1993). GROWTH-INHIBITION OF T47D HUMAN BREAST-CANCER CELLS BY THE NEW ANTIAROMATASE STEROID 3-METHYLENE-1,4-ANDROSTADIEN-17-ONE. International Journal of Oncology, 3, 891-896. https://doi.org/10.3892/ijo.3.5.891
MLA
GIROUARD, F., TAN, L."GROWTH-INHIBITION OF T47D HUMAN BREAST-CANCER CELLS BY THE NEW ANTIAROMATASE STEROID 3-METHYLENE-1,4-ANDROSTADIEN-17-ONE". International Journal of Oncology 3.5 (1993): 891-896.
Chicago
GIROUARD, F., TAN, L."GROWTH-INHIBITION OF T47D HUMAN BREAST-CANCER CELLS BY THE NEW ANTIAROMATASE STEROID 3-METHYLENE-1,4-ANDROSTADIEN-17-ONE". International Journal of Oncology 3, no. 5 (1993): 891-896. https://doi.org/10.3892/ijo.3.5.891