Novel curcumin analogue IHCH exhibits potent anti‑proliferative effects by inducing autophagy in A549 lung cancer cells.
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.
College of Bioengineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
Guang-Zhou
GZ
Zhou
College of Bioengineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
Su-Li
SL
Xu
College of Chemistry and Chemical Engineering, Henan University of Technology, Zhengzhou, Henan 450001, P.R. China.
Gang-Chun
GC
Sun
The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan 450008, P.R. China.
Xiao-Bing
XB
Chen
D000730:Androstadienes / Q000494:pharmacology; D000935:Antifungal Agents / Q000494:pharmacology; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003474:Curcumin / Q000737:chemistry / Q000633:toxicity*; D003512:Cyclohexanones / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000633:toxicity*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D000077191:Wortmannin
C000594382:2-(1H-indol-3-yl)methylene-6-(4-hydroxy-3-methoxybenzylidene)cyclohexanone; D000730:Androstadienes; D000935:Antifungal Agents; D003512:Cyclohexanones; D007211:Indoles; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; D003474:Curcumin; D000077191:Wortmannin