demethoxycurcumin and Prostatic-Neoplasms

Curcumin (CUR) is a natural agent that has been demonstrated to effectively inhibit prostate cancer growth. However, natural CUR is relatively unstable and can be easily degraded in vivo. Therefore, it is essential to develop other stable curcuminoids. Demethoxycurcumin (DMC) is a candidate that has been verified in several tumor types and has potential for the treatment of prostate cancer. In the present study, we investigated the effects of DMC on proliferation, apoptosis and migration of PC-3 cells. MTT assay results indicated that DMC inhibited PC-3 cell viability in a dose- and time-dependent manner, and DMC induced G2/M phase arrest. Furthermore, PC-3 cells in DMC-treated groups had a higher apoptotic rate compared with DMSO-treated control. This effect may be due to the activation of the caspase-3 pathway. In DMC-treated groups, migrating and invasive cells were dramatically reduced (P<0.05). The activity of MMP-2, which is correlated with migration and invasion was also suppressed by DMC. These results indicated that DMC may inhibit PC-3 cell migration and invasion partially by affecting MMP-2 activity. In conclusion, DMC significantly inhibits proliferation, migration and invasion of cultured PC-3 cells, and this study may provide evidence for future in vivo studies and clinical use.

Topics: Antineoplastic Agents; Apoptosis; Caspase 3; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Curcumin; Diarylheptanoids; Enzyme Activation; Humans; M Phase Cell Cycle Checkpoints; Male; Matrix Metalloproteinase 2; Proliferating Cell Nuclear Antigen; Prostatic Neoplasms

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.

Topics: Aminoimidazole Carboxamide; AMP-Activated Protein Kinases; Antineoplastic Agents, Phytogenic; Caspase 3; Cell Line, Tumor; Cell Proliferation; Curcuma; Curcumin; Diarylheptanoids; Down-Regulation; ErbB Receptors; Fatty Acid Synthase, Type I; HSP70 Heat-Shock Proteins; Humans; Male; Phosphorylation; Prostatic Neoplasms; Protein Tyrosine Phosphatase, Non-Receptor Type 11; Proto-Oncogene Proteins c-cbl; Ribonucleotides