Curcumin Suppresses Proliferation and Migration of MDA-MB-231 Breast Cancer Cells through Autophagy-Dependent Akt Degradation

• Published in: PloS one Vol. 11; no. 1; p. e0146553
• Main Authors: Guan, Feng, Ding, Youming, Zhang, Yemin, Zhou, Yu, Li, Mingxin, Wang, Changhua
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 11.01.2016; Public Library of Science (PLoS)
• Subjects: 1-Phosphatidylinositol 3-kinase; Activation; Adenoviruses; AKT protein; Antineoplastic Agents - pharmacology; Apoptosis; Autophagy; Autophagy (Cytology); Autophagy - drug effects; Bioactive compounds; Biodegradation; Breast cancer; Breast Neoplasms - metabolism; Cancer; Cell cycle; Cell death; Cell growth; Cell Line, Tumor; Cell migration; Cell Movement - drug effects; Cell proliferation; Cell Proliferation - drug effects; Complications and side effects; Curcumin; Curcumin - pharmacology; Deactivation; Degradation; Dosage and administration; Drug therapy; Female; Gene Expression Regulation, Neoplastic - drug effects; Genetic aspects; Humans; Inactivation; Inhibition; Kinases; Lysosomal protein; Phagocytosis; Pharmacology; Physiological aspects; Proteasomes; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Quantitative analysis; Signaling; Ubiquitin; China; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0146553

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.