Novel curcumin analogue IHCH exhibits potent anti-proliferative effects by inducing autophagy in A549 lung cancer cells

Abstract

Curcumin is a natural polyphenolic compound that exhibits strong antioxidant and anticancer activities; however, low bioavailability has restricted its application in chemotherapeutic trials. The present study aimed to investigate the anticancer effect of the novel curcumin derivative 2E,6E-2-(1H-indol-3-yl) methylene)-6-(4-hydroxy-3-methoxy benzylidene)- cyclohexanone (IHCH) on A549 lung cancer cells. Cells were treated with IHCH at different concentrations (1-40 μM) for different time periods (1-36 h). Microscopic analysis revealed that IHCH inhibited A549 cell growth and induced the formation of characteristic autophagolysosomes in a dose- and time-dependent manner. Furthermore, the inhibitory rate of IHCH (40 μM) on A549 cell viability was 77.34% after 36 h of treatment. Acridine orange staining revealed an increase in autophagic vacuoles in the IHCH-treated A549 cells. Monodansylcadaverine staining was used to analyze autophagy rate. Immunocytochemistry revealed an increase in light chain (LC) 3 protein expression in the IHCH-treated cells and western blot analysis detected the conversion of LC3-I to LC3-II, as well as the recruitment of LC3 to autophagosomes in the cytoplasmatic compartment, suggesting the occurrence of autophagy. These findings show that IHCH induced autophagy in A549 cells, which is a novel cell death mechanism induced by curcumin derivatives.