The Polyphenolic Compound Curcumin Conjugation with an Alkyne Moiety in the Process of Autophagy
Abstract
Curcumin is a hydrophobic polyphenol derived from turmeric: the rhizome of the herb Curcumalonga. Autophagy is an evolutionarily conserved process, in which cellular proteins and organelles are engulfed in autophagosome and then fuses with lysosome for degradation. Our previous study showed that Curcumin activates lysosome and induce autophagy through inhibition of AKT (protein kinase K, PKB)-mammalian target of rapamycin (mTOR) pathway. But whether Curucmin affects the fusion of autophagosome-lysosome is still not clear. Here, we used Curcumin-probe conjugation with an alkyne moiety to label mouse embryonic fibroblasts (MEFs) and found that Curcumin targets autophagy-related proteins, enhances autophagic flux and activates lysosome in cells. Moreover, Curcumin treatment promotes the fusion of autophasosome-lysosome in MEFs. Second, the enhanced fusion of autophagosome-lysosome is attributed to mTOR suppression. Third, blockage of the autophagosome-lysosome fusion leads to cell growth inhibition by Curcumin. Taken together, data from our study indicates the importance of the fusion of autophagosome-lysosome in Curcumin-induced autophagy, which may facilitate the development of Curcumin as a potential therapeutic agent for oxidative stress-related diseases.
