title: 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.
authors: Department of General Surgery, E-Da Hospital, I-Shou University , Kaohsiung, Taiwan.
authors: Chao-Ming
authors: CM
authors: Hung
authors: Yun-Hsuan
authors: YH
authors: Su
authors: Hui-Yi
authors: HY
authors: Lin
authors: Jia-Ni
authors: JN
authors: Lin
authors: Liang-Chih
authors: LC
authors: Liu
authors: Chi-Tang
authors: CT
authors: Ho
authors: Tzong-Der
authors: TD
authors: Way
mesh_terms: D055372:AMP-Activated Protein Kinases; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D030024:Curcuma / Q000737:chemistry; D003474:Curcumin / Q000031:analogs & derivatives* / Q000494:pharmacology; D036381:Diarylheptanoids; D015536:Down-Regulation; D066246:ErbB Receptors / Q000378:metabolism*; D054890:Fatty Acid Synthase, Type I / Q000378:metabolism; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11 / Q000037:antagonists & inhibitors; D050721:Proto-Oncogene Proteins c-cbl / Q000378:metabolism; D012265:Ribonucleotides / Q000494:pharmacology
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D036381:Diarylheptanoids; D018840:HSP70 Heat-Shock Proteins; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; C518729:FASN protein, human; D054890:Fatty Acid Synthase, Type I; D050721:Proto-Oncogene Proteins c-cbl; C512478:EGFR protein, human; D066246:ErbB Receptors; D055372:AMP-Activated Protein Kinases; D054592:Protein Tyrosine Phosphatase, Non-Receptor Type 11; D053148:Caspase 3; C067419:CBL protein, human; C031143:AICA ribonucleotide; D003474:Curcumin; C050229:demethoxycurcumin