Interactive effects of 9-cis-retinoic acid and androgen on proliferation, differentiation, and apoptosis of LNCaP prostate cancer cells

Abstract

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 mol/l. 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. 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.

Characterizing isoform switching events in esophageal adenocarcinoma

“…80,81 Studies have also pointed out that cancer cells treated with 9-cis-retinoic acid induce apoptosis and inhibit cancer cell growth both in vitro and in vivo. 82,83 Moreover, retinoic acid receptor RARb, was shown to act as a tumor suppressor in lung cancer. 84 In BE patients with…”

Metabolomics and Proteomics Reveal the Variation of Substances in Apheresis Platelets during Storage and Their Effects on Cancer Cell Proliferation

“…We were able to confirm that the day-0 and day-5 stored APs showed significantly different metabolomics in their supernatants, and found that the upregulated metabolites retinoate and 9-cis-retinoic acid in day-5 stored AP supernatants were enriched in cancer-related KEGG pathways. There are also studies that indicate that retinoate and 9-cis-retinoic acid are inversely related to malignant features [22][23][24][25]. Some reports state that retinoate and 9-cis-retinoic acid both participate in the regulation of the immune system.…”

Metabolomics research on potential role for 9‐cis‐retinoic acid in breast cancer progression

“…It participates in retinol metabolism and can also be converted to 9‐cis‐retinal by specific regulatory enzymes. 9‐cisRA which binds to both retinoic acid receptors (RAR) and nuclear retinoid X receptors (RXR) prevented prostate carcinogenesis in rats, reduced growth and induced apoptosis of human prostate cancer cells in a dose‐dependent method . 9‐cisRA induced the downregulation of P‐glycoprotein, the overexpression of which develops MDR phenotype in L1210 lymphocytic leukemia cells .…”

“…9-cisRA which binds to both retinoic acid receptors (RAR) and nuclear retinoid X receptors (RXR) prevented prostate carcinogenesis in rats, reduced growth and induced apoptosis of human prostate cancer cells in a dose-dependent method. 33 9-cisRA induced the downregulation of P-glycoprotein, the overexpression of which develops MDR phenotype in L1210 lymphocytic leukemia cells. 34 It also directly retarded the cell cycle in a concentration-and time-dependent method in NCI-H295R adrenocortical cancer cells as well as reduced tumor growth in the in vivo xenograft model.…”