Inhibition of Wnt/β-catenin signaling mediates ursolic acid-induced apoptosis in PC-3 prostate cancer cells.
Journal Title: Pharmacological Reports - Year 2013, Vol 65, Issue 5
Abstract
Background: Ursolic acid, a pentacyclic triterpenoid, is known to exert antitumor activity in breast, lung, liver and colon cancers. Nonetheless, the underlying mechanism of ursolic acid in prostate cancer cells still remains unclear. To investigate the antitumor mechanism, the apoptotic mechanism of ursolic acid via Wnt/β-catenin signaling was examined in PC-3 prostate cancer cells. Methods: Cytotoxicity assay, flow cytometry, immunofluorescence assay and western blotting were performed. Results: Ursolic acid showed cytotoxicity against PC-3, LNCaP and DU145 prostate cancer cells with IC50 of 35 μM, 47 μM and 80 μM, respectively. Also, ursolic acid significantly increased the number of ethidium homodimer stained cells and apoptotic bodies, and dose-dependently enhanced the sub-G1 apoptotic accumulation in PC-3 cells. Consistently, western blotting revealed that ursolic acid effectively cleaved poly (ADP-ribose) polymerase (PARP), activated caspase-9 and -3, suppressed the expression of survival proteins such as Bcl-XL, Bcl-2 and Mcl-1, and upregulated the expression of Bax in PC-3 cells. Interestingly, ursolic acid suppressed the expression of Wnt5α/β and β-catenin, and enhanced the phosphorylation of glycogen synthase kinase 3 β (GSK3β). Furthermore, the GSK3β inhibitor SB216763 or Wnt3a-conditioned medium (Wnt3a-CM) reversed the cleavages of caspase-3 and PARP induced by ursolic acid in PC-3 cells. Conclusions: Our findings suggest that ursolic acid induces apoptosis via inhibition of the Wnt5/β-catenin pathway and activation of caspase in PC-3 prostate cancer cells. These results support scientific evidence that medicinal plants containing ursolic acid can be applied to cancer prevention and treatment as a complement and alternative medicine (CAM) agent.
Authors and Affiliations
Ji-Hyuk Park, Hee-Young Kwon, Eun Sohn, Kyung Kim, Bonglee Kim, Soo-Jin Jeong, Jun Song, Jin Koo, Sung-Hoon Kim
Keywords
Related Articles
- EP ID EP131274
- DOI -
- Views 96
- Downloads 0
Proton pump (H(+)/K(+)-ATPase) inhibitors weaken the protective effect of alendronate on bone mechanical properties in estrogen-deficient rats.
Background: Alendronate can induce esophagitis and stomach ulceration requiring the concurrent use of drugs which decrease HCl production. The aim of the present study was to investigate the effect of concurrent administ...
Different effects of nitric oxide synthase inhibitors on convulsions induced by nicotine in mice.
Acute intraperitoneal (ip) administration of N(G)-nitro-L-arginine (NNA, 10, 20 and 40 mg/kg), a non-selective nitric oxide synthase (NOS) inhibitor, significantly and dose-dependently decreased the incidence of convulsi...
Constitutive activity of beta-adrenergic receptors in C6 glioma cells.
Alprenolol and propranolol (0.001-10 muM) significantly and concentration-dependently inhibited both isoprenaline-driven and basal (non-stimulated) cyclic adenosine monophosphate (cAMP) accumulation in the rat C6 glioma...
Lipid peroxidation and antioxidant protection in patients during acute depressive episodes and in remission after fluoxetine treatment.
Increasing numbers of studies indicate that free radicals and their derivatives play a role in some neuropsychiatric disorders, such as depression. The aim of this study was to investigate the activities of antioxidant e...
Effect of blockage of the endocannabinoid system by CB(1) antagonism on cardiovascular risk.
The endocannabinoid system is a crucial player in the inflammatory processes underlying atherosclerosis. Recently, basic research studies and animal models have strongly supported the role of the endocannabinoid system n...