Demethoxycurcumin Modulates Prostate Cancer Cell Proliferation via AMPK-Induced Down-regulation of HSP70 and EGFR

Abstract

Curcumin (Cur), demethoxycurcumin (DMC), and bisdemethoxycurcumin (BDMC) are major forms of curcuminoids found in the rhizomes of turmeric. This study examined the effects of three curcuminoid analogues on prostate cancer cells. The results revealed that DMC demonstrated the most efficient cytotoxic effects on prostate cancer PC3 cells. DMC activated AMPK and in turn decreased the activity and/or expression of lipogenic enzymes, such as fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC). AICAR, an AMPK activator, and DMC down-regulated heat shock protein (HSP) 70 and increased the activity of the pro-apoptotic effector, caspase-3. In addition, DMC sustained epidermal growth factor receptor (EGFR) activation by suppressing the phosphatases PP2a and SHP-2. DMC also increased the interaction between EGFR and Cbl and induced the tyrosine phosphorylation of Cbl. The results suggest that DMC may have antitumor effects on prostate cancer cells via AMPK-induced down-regulation of HSP70 and EGFR.

Demethoxycurcumin inhibited human epithelia ovarian cancer cells’ growth via up-regulating miR-551a

“…DMC inhibited prostate cancer PC-3 cells' proliferation via mitogen-activated protein kinase (MAPK) pathway and displayed the most effective among the three compounds in prostate cancer PC-3 cells. 20 Similarly, DMC led to G2/M arrest and induced apoptosis in human glioblastoma U87 cells. 21 Moreover, DMC induced apoptosis by increasing the level of reactive oxygen species and the activating of caspase-3 in human renal carcinoma caki cells.…”

Mechanism of dihydroartemisinin-induced apoptosis in prostate cancer PC3 cells: An iTRAQ-based proteomic analysis

“…In the present study, DHA significantly decreased HSP70 expression and induced apoptosis in PC3 cells. Although the mechanism of apoptosis induced by DHA is poorly understood, several lines of evidence have shown inhibition of HSP70 expression results in apoptosis of cancer cells, and/or sensitizes cells to anticancer therapy in prostate cancer lines PC3, PC3M, DU145, LNCaP, JCA-1, and 22RV1 [87][88][89][90][91][92][93][94][95]. Our protein interaction network analysis suggests that HSP70 should function as both a chaperone and a modulator of cell signaling to participate in several biological processes in response to the cytotoxicity of DHA in PC3 cells.…”

Demethoxycurcumin Modulates Human P-Glycoprotein Function via Uncompetitive Inhibition of ATPase Hydrolysis Activity

“…Several studies also showed that DMC possessed the most efficient cytotoxic effects toward breast cancer and prostate cancer cells. 18,31,32 It was reported that DMC may activate AMPK and thus inhibit energy metabolic and oncogenic signaling pathways in triple-negative breast cancer cells. 31 It was also shown in another study that DMC may down-regulate HSP70 and EGFR and further influence the proliferation of prostate cancer cells.…”