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.
Highlights
IntroductionCurcumin (diferuloylmethane), a polyphenol isolated from the rhizome of an East Indian plant Curcuma longa (commonly known as turmeric), has been used in medicine for centuries in Asia
Curcumin, a polyphenol isolated from the rhizome of an East Indian plant Curcuma longa, has been used in medicine for centuries in Asia
To confirm the anticancer effects of curcumin, we firstly tested its impacts on cell proliferation and apoptosis in MDA-MB-231 breast cancer cells
Summary
Curcumin (diferuloylmethane), a polyphenol isolated from the rhizome of an East Indian plant Curcuma longa (commonly known as turmeric), has been used in medicine for centuries in Asia. Due to its anti-oxidant and anti-inflammatory properties, curcumin has been proposed as a potential candidate for the prevention and/or treatment of some diseases such as neurodegenerative disorders, inflammatory diseases, cardiovascular diseases, and other chronic diseases. Curcumin presents strong anticancer properties by regulating cell cycle, apoptosis and survival, proliferation, angiogenesis, invasion, and metastasis [1,2,3]. Its relative safety and cost considerations make curcumin a potential new treatment option for various cancers.
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