Bioflavonoids, type II [H-3]estradiol binding sites and prostatic cancer cell proliferation

  • Authors:
    • B Markaverich
    • M Alejandro
  • View Affiliations

  • Published online on: December 1, 1997     https://doi.org/10.3892/ijo.11.6.1311
  • Pages: 1311-1319
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Abstract

Previous studies from this laboratory have shown that bioflavonoids including luteolin and quercetin possess antiestrogenic activity in the female reproductive tract and appear to elicit this activity by interaction with type II [H-3]estradiol binding sites in the cell nucleus. Studies by a number of laboratories including our own have shown that type II sites are present in the rodent prostate gland and therefore, we suspected that administration of bioflavonoids such as luteolin may antagonize prostate growth through type LT site binding interactions as well. The studies presented in this report demonstrate that the mouse prostatic tissue does contain nuclear type II sites and that oral administration of luteolin for 14 days results in a significant (p<0.01) reduction in prostatic weight in intact male mice without significant effects on the seminal vesicular, testis or body weights of these animals. These results suggest that luteolin is a prostate specific antagonist under these experimental conditions. In vitro studies with LNCaP and PC-3 human prostate cancer cell lines demonstrated that luteolin treatment resulted in a dose dependent inhibition of prostate cancer cell proliferation which was maximum 4-8 days following treatment. Whole cell binding studies demonstrated that both LNCaP and PC-3 cells contained very high concentrations of type II [H-3]estradiol binding sites (>200,000 sites/cell) relative to levels previously reported for other tissues and cells and luteolin was capable of interacting with these sites in prostate cancer cells. In fact, there was a direct correlation between the type II site occupancy by luteolin and the inhibition of LNCaP or PC-3 prostatic cancer cell proliferation by this bioflavonoid. Flow cytometric analysis revealed that luteolin treatment caused an accumulation of LNCaP cells in G(2)/M (p<0.01) and reduced the fractions of LNCaP cells in S-phase undergoing apoptosis (p<0.01). Similarly, luteolin treatment also arrested PC-3 cells in G(2)/M (p<0.01) and reduced the proportion of cells in G(0)/G(1) (p<0.05). This being the case, it is not surprising that this bioflavonoid also blocked the growth of subcutaneous PC-3 cell xenografts in athymic nude mice. These data demonstrate that naturally occurring type TI site antagonists such as luteolin are capable of inhibiting normal and malignant prostatic cell growth and proliferation in vitro and in viva and may possess prophylactic as well as therapeutic activities against prostatic proliferative diseases including benign prostatic hyperplasia (BPH) and prostate cancer.

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December 1997
Volume 11 Issue 6

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

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Spandidos Publications style
Markaverich B and Markaverich B: Bioflavonoids, type II [H-3]estradiol binding sites and prostatic cancer cell proliferation. Int J Oncol 11: 1311-1319, 1997
APA
Markaverich, B., & Markaverich, B. (1997). Bioflavonoids, type II [H-3]estradiol binding sites and prostatic cancer cell proliferation. International Journal of Oncology, 11, 1311-1319. https://doi.org/10.3892/ijo.11.6.1311
MLA
Markaverich, B., Alejandro, M."Bioflavonoids, type II [H-3]estradiol binding sites and prostatic cancer cell proliferation". International Journal of Oncology 11.6 (1997): 1311-1319.
Chicago
Markaverich, B., Alejandro, M."Bioflavonoids, type II [H-3]estradiol binding sites and prostatic cancer cell proliferation". International Journal of Oncology 11, no. 6 (1997): 1311-1319. https://doi.org/10.3892/ijo.11.6.1311