title: Curcumin Suppresses Proliferation and Migration of MDA-MB-231 Breast Cancer Cells through Autophagy-Dependent Akt Degradation.
abstract: Previous studies have evidenced that the anticancer potential of curcumin (diferuloylmethane), a main yellow bioactive compound from plant turmeric was mediated by interfering with PI3K/Akt signaling. However, the underlying molecular mechanism is still poorly understood. This study experimentally revealed that curcumin treatment reduced Akt protein expression in a dose- and time-dependent manner in MDA-MB-231 breast cancer cells, along with an activation of autophagy and suppression of ubiquitin-proteasome system (UPS) function. The curcumin-reduced Akt expression, cell proliferation, and migration were prevented by genetic and pharmacological inhibition of autophagy but not by UPS inhibition. Additionally, inactivation of AMPK by its specific inhibitor compound C or by target shRNA-mediated silencing attenuated curcumin-activated autophagy. Thus, these results indicate that curcumin-stimulated AMPK activity induces activation of the autophagy-lysosomal protein degradation pathway leading to Akt degradation and the subsequent suppression of proliferation and migration in breast cancer cell.
authors.affiliation: Department of Pathophysiology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Guan
authors.affiliation: Department of Hepatobiliary & Laparascopic Surgery, Wuhan University Renmin Hospital, Wuhan, 430060, China.
authors.forename: Youming
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Pathophysiology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, China.
authors.forename: Yemin
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Hepatobiliary & Laparascopic Surgery, Wuhan University Renmin Hospital, Wuhan, 430060, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Department of Pathophysiology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, China.
authors.forename: Mingxin
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Pathophysiology, Wuhan University School of Basic Medical Sciences, Wuhan, 430071, China.
authors.forename: Changhua
authors.initials: C
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D051057:Proto-Oncogene Proteins c-akt; D003474:Curcumin