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

Abstract

Curcumin is a component of turmeric and is isolated from the rhizomes of the plant Curcuma longa. Curcumin was reported to have therapeutic effects on prostate cancer. Yet the molecular mechanism of curcumin remains unclear. In this study, mouse prostate cancer xenograft model was established and subjected to curcumin treatment. GST-c-Jun pull down kinase assays were performed to study the phospho-c-Jun level. Cell Counting Kit-8 assay kit was utilized to detect the cell viability. Immunoblotting and qRT-PCR were performed for target gene expression analysis. Curcumin inhibited growth of prostate cancer in vivo as well as promoted apoptosis of LNCaP cells in vitro. Curcumin inhibited JNK pathway and repressed H3K4me3 in LNCaP cells. Combined use of curcumin and JQ-1 inhibited the prostate cancer efficiently. In conclusion, curcumin inhibits JNK pathway and plays a role in epigenetic regulation of prostate cancer cells by repressing H3K4me3.

Fluctuations of Histone Chemical Modifications in Breast, Prostate, and Colorectal Cancer: An Implication of Phytochemicals as Defenders of Chromatin Equilibrium

“…Zhao et al evaluated the impact of CUR on suppression of LNCaP cells via inhibition of the c-Jun-N-terminal kinase (JNK) signaling pathway. Acquired data suggested a decreased level of H3K4me3 in PC cells connected to the reduction of the JNK pathway [147]. Importantly, mixtures of phytochemicals in plants and their synergic effects showed antioxidant and antineoplastic properties in cancer.…”

Curcumin against Prostate Cancer: Current Evidence

“…Treatment of LNCaP cells with curcumin induced apoptosis paired with lower phosphorylation of c-Jun NH2-terminal kinase (JNK) and c-Jun and lower levels of BCL-2 mRNA [86]. At the epigenetic level, curcumin stimulated the reduction of trimethylation of H3K4 (H3K4me3) leading to repressed gene expression, although no significant changes were observed in H3K27 gene expression [86].…”

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

“…Suppressed tumour progression of AP-1, which indicated by the reduced colony forming ability in soft agar [92,103] PC-3 Exhibited anti-cancer effects by impeding AP-1 protein [108] LNCaP Promoted cell cycle arrest and apoptosis by regulating the level of c-Jun proteins, which is activated via phosphorylation by the c-Jun amino terminal kinase (JNK) [116,117] Increased apoptotic cell death mediated by caspase activation and the loss of mitochondrial membrane integrity [128] PC-3 Induced the apoptosis proteins by inhibition of NF-κB and NF-κB-regulated anti-apoptotic genes products through suppression of Akt [113] Nutrients 2020, 12, 679 8 of 34 Inhibited cell proliferation and migration by restoring miR-143/miR-145 cluster expression [135,136] Abbreviations: Androgen receptor (AR) signalling, Activating protein-1 (AP-1), Phosphatidylinositol 3-kinases/the serine/threonine kinase (PI3K/Akt/mTOR), Wingless (Wnt)/ß-catenin signalling, and molecular targets; Nuclear factor kappa-B (NF-κB), B-cell lymphoma 2 (Bcl-2) and Cyclin D1.…”

“…Other studies reported that curcumin exhibits its anti-cancer effects by significantly impeding AP-1 protein in AIPC (PC-3) cells [108]. Besides, curcumin treatment is able to promote cell cycle arrest and apoptosis in ADPC (LNCaP) cells by regulating the level of c-Jun proteins, an important member of the AP-1 complex which is primarily activated via phosphorylation by the c-Jun amino terminal kinase (JNK) [116,117]. Furthermore, curcumin has shown the ability to reduce cell proliferation and migration of ADPC (LNCaP) cells by suppressing the activation of AP-1 that are stimulated by hydrogen peroxide [118].…”