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. 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 10−7 mol/l. Treatment of cells with 10−6 mol/l 9cRA inhibited 5α-dihydroxytestosterone (DHT)-stimulated proliferation, the effect of which was maximal at 10−9 mol/l DHT. Treatment of DHT (10−9 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. 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.
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
* Jillian N. Eskra and Jan W. Kuiper contributed equally to the writing of this article.
Jan W. Kuiper: Wytemaweg 80, 3015 CN Rotterdam, The Netherlands
Nur Özten is a senior author.
Correspondence to Maarten C. Bosland, PhD, Department of Pathology, University of Illinois at Chicago, 840 South Wood Street, Room 130 CSN, Chicago, IL 60612, USA Tel: +1 312 355 3724; fax: +1 312 996 7586; e-mail: email@example.com
Received July 23, 2015
Accepted January 9, 2016