Anti‐Lung Cancer Activities of 1,2,3‐Triazole Curcumin Derivatives via Regulation of the MAPK/NF‐κB/STAT3 Signaling Pathways
Tai Xin Zhi, Kai Qiang Liu, Kun Cai, Yu Chao Zhao, Zhen Wang Li, Xin Wang, Xin Hua He, Xian Yu Sun
Abstract
Abstract In this study, a series of curcumin derivatives containing 1,2,3‐triazole were designed and synthesized, and their inhibitory activities against the proliferation of lung cancer cells were studied. Compound 5 k (3,4‐dichlorobenzyltriazole methyl curcumin) had the best activity against A549 cells, with a half‐maximal inhibitory concentration (IC 50 ) of 2.27 μM, which was approximately 10 times higher than that of the lead curcumin and higher than that of gefitinib (IC 50 =8.64 μM). Western blotting revealed that 5 k increased the phosphorylation levels of p38, c‐Jun N‐terminal kinase (JNK), and extracellular signal‐regulated kinase (ERK). Compound 5 k also promoted the expression of the inhibitor of nuclear factor‐κB (IκBα) and decreased that of nuclear factor‐κB (NF‐κB), signal transducer and activator of transcription 3 (STAT3), and β‐catenin. Therefore, 5 k suppresses A549 cell proliferation by activating the mitogen‐activated protein kinases and suppressing NF‐κB/STAT3 signaling pathways. So, 5 k can potentially be used for treating non‐small cell lung cancer.