Targeting multiple pro-apoptotic signaling pathways with curcumin in prostate cancer cells

Abstract

Curcumin, an extract from the turmeric rhizome (Curcuma longa), is known to exhibit anti-inflammatory, antioxidant, chemopreventive and antitumoral activities against aggressive and recurrent cancers. Accumulative data indicate that curcumin may induce cancer cell death. However, the detailed mechanism underlying its pro-apoptotic and anti-cancer effects remains to be elucidated. In the present study, we examined the signaling pathways triggered by curcumin, specifically, the exact molecular mechanisms of curcumin-induced apoptosis in highly metastatic human prostate cancer cells. The effect of curcumin was evaluated using for the first time in prostate cancer, a gel-free shotgun quantitative proteomic analysis coupled with Tandem Mass Tag isobaric labeling-based-signaling networks. Results were confirmed at the gene expression level by qRT-PCR and at the protein expression level by western blot and flow cytometry. Our findings revealed that curcumin induced an Endoplasmic Reticulum stress-mediated apoptosis in PC3. The mechanisms by which curcumin promoted cell death in these cells were associated with cell cycle arrest, increased reactive oxygen species, autophagy and the Unfolded Protein Response. Furthermore, the upregulation of ER stress was measured using key indicators of ER stress: Glucose-Regulated Protein 78, Inositol-Requiring Enzyme 1 alpha, Protein Disulfide isomerase and Calreticulin. Chronic ER stress induction was concomitant with the upregulation of pro-apoptotic markers (caspases 3,9,12) and Poly (ADP-ribose) polymerase. The downregulated proteins include anti-apoptotic and anti-tumor markers, supporting their curcumin-induced pro-apoptotic role in prostate cancer cells. Taken together, these data suggest that curcumin may serve as a promising anticancer agent by inducing a chronic ER stress mediated cell death and activation of cell cycle arrest, UPR, autophagy and oxidative stress responses.

Curcumin suppressed the prostate cancer by inhibiting JNK pathways via epigenetic regulation

“…The tumorigenicity of curcumin‐treated HuPCaSCs in nude mice was significantly reduced . Curcumin induced an endoplasmic reticulum stress‐mediated apoptosis in highly metastatic human prostate cancer cells PC3 . It suggests that curcumin may serve as a promising anticancer agent by inducing a chronic endoplasmic reticulum (ER) stress mediated cell death and activation of cell cycle arrest, unfolded protein response, autophagy, and oxidative stress responses .…”

“…Curcumin induced an endoplasmic reticulum stress‐mediated apoptosis in highly metastatic human prostate cancer cells PC3 . It suggests that curcumin may serve as a promising anticancer agent by inducing a chronic endoplasmic reticulum (ER) stress mediated cell death and activation of cell cycle arrest, unfolded protein response, autophagy, and oxidative stress responses . In addition, curcumin induces apoptosis and protective autophagy in castration‐resistant prostate cancer cells, which are at least partially dependent on its iron‐chelating properties .…”

Mechanism of Anti-Cancer Activity of Curcumin on Androgen-Dependent and Androgen-Independent Prostate Cancer

“…Besides, curcumin was shown capable of decreasing intracellular prostate testosterone level in ADPC (LNCaP) cells and in transgenic adenocarcinoma of the mouse prostate (TRAMP) model, thereby prevent the activation of AR by downregulating the expression of steroidogenic acute regulatory proteins, CYP11A1 and HSD3B2 [102,150]. Moreover, curcumin treatment against AIPC (PC-3) cells also alter the over-expressed heat shock protein (Hsp90), resulting in the reduction of AR availability [104]. Curcumin also shows positive outcomes when tested in animal models, where it delays the tumour growth and suppresses AR expression in ADPC (LNCaP) xenograft model [105].…”

The Ginger Prophecy; A Review of the Underexplored Genus, Hedychium against Cancer

“…Alpinia officinarum A549 [53] Caffeic acid, apigenin, curcumin, pinnocambrin Alpinia pricei (rhizome) CH 27, HL 60, A 549 [54] Curcumin Curcuma kwangsiensis LoVa, SW480 [60] Curcumin Curcuma longa A549 [61] , PC3 [62] , melanoma [63] Α-zingiberene, gingerol Zingiber officinale (rhizome) HeLa, SiHa [64] , HCT116, SW480, LoVo [65] , MDA-MB-231 [66] Zerumbone…”