Research: ESKRA and COLLEAGUES,

Listed in Issue 259

Abstract

ESKRA and COLLEAGUES, 1. aDepartment of Pathology, University of Illinois at Chicago, Chicago, Illinois Departments of bEnvironmental Medicine cUrology, New York University School of Medicine, New York, New York, USA dFaculty of Pharmacy, Bezmiâlem Vakif University, Fatih, Istanbul, Turkey studied the interactive effects of 9-cis-retinoic acid and androgen on proliferation, differentiation, and apoptosis of LNCaP prostate cancer cells.

Background

9-cis-Retinoic acid (9cRA), which binds to both retinoic acid receptors and retinoic X receptors, inhibits prostate cancer induction in rats and reduces growth of prostate cancer cells. However, the nature of this growth inhibition and the interactive influence of androgens are not well defined and are the subject of this report.

Methodology

LNCaP and PC-3 cells were cultured and treated with a range of 9cRA concentrations for 3-6 days in the absence or presence of 5α-dehydrotestosterone. 9cRA inhibited cell proliferation in a dose-dependent manner, plateauing at 10 mol/l.

Results

Treatment of cells with 10 mol/l 9cRA inhibited 5α-dihydroxytestosterone (DHT)-stimulated proliferation, the effect of which was maximal at 10 mol/l DHT. Treatment of DHT (10 mol/l)-exposed cells with 9cRA caused a dose-dependent increase in prostate-specific antigen in the medium after 6 days, but not 3 days. 9cRA caused a dose-dependent increase in apoptotic cells stained with H33258 after 3 days, but not 6 days; however, on using flow cytometry, apoptosis was apparent at both 3 and 6 days. Flow cytometry also revealed interference of G0/G1 to S phase transition by 9cRA. Inhibition by 9cRA of anchorage-independent growth of PC-3 cells was also found; LNCaP cells did not grow colonies in soft agar. 9cRA inhibited growth and induced differentiation of human LNCaP prostate cancer cells in vitro and inhibited anchorage-independent growth of PC-3 cells.

Conclusion

Because 9cRA and 13-cis-retinoic acid, which is retinoic acid receptor-selective, prevent prostate carcinogenesis in rats, and 13-cis-retinoic acid also inhibits growth of human prostate cancer cells, the RAR is a potential molecular target for prostate cancer prevention and therapy.

References

Eskra JN1, Kuiper JW, Walden PD, Bosland MC, Özten N. Interactive effects of 9-cis-retinoic acid and androgen on proliferation, differentiation, and apoptosis of LNCaP prostate cancer cells. Eur J Cancer Prev. 26(1):71-77. Jan 2017.

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