Xanthatin Induces Cell Cycle Arrest at G2/M Checkpoint and Apoptosis via Disrupting NF-κB Pathway in A549 Non-Small-Cell Lung Cancer Cells

Molecules

Lei Zhang¹  Junshan Ruan¹  Linggeng Yan¹  Weidong Li¹  Yu Wu¹  Li Tao¹  Feng Zhang¹  Shizhong Zheng¹  Aiyun Wang¹ 

[1]Department of Clinical Pharmacy, College of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210029, China

关键词: xanthatin;    non-small-cell lung cancer;    cytotoxicity;    cell cycle;    apoptosis;   

DOI  :  10.3390/molecules17043736

来源: mdpi

【 摘 要 】

Xanthatin, a natural sesquiterpene lactone, has significant antitumor activity against a variety of cancer cells, yet little is known about its anticancer mechanism. In this study, we demonstrated that xanthatin had obvious dose-/time-dependent cytotoxicity against the human non-small-cell lung cancer (NSCLC) cell line A549. Flow cytometry analysis showed xanthatin induced cell cycle arrest at G2/M phase. Xanthatin also had pro-apoptotic effects on A549 cells as evidenced by Hoechst 33258 staining and annexin V-FITC staining. Mechanistic data revealed that xanthatin downregulated Chk1, Chk2, and phosphorylation of CDC2, which contributed to the cell cycle arrest. Xathatin also increased total p53 protein levels, decreased Bcl-2/Bax ratio and expression of the downstream factors procaspase-9 and procaspase-3, which triggered the intrinsic apoptosis pathway. Furthermore, xanthatin blocked phosphorylation of NF-κB (p65) and IκBα, which might also contribute to its pro-apoptotic effects on A549 cells. Xanthatin also inhibited TNFα induced NF-κB (p65) translocation. We conclude that xanthatin displays significant antitumor effects through cell cycle arrest and apoptosis induction in A549 cells. These effects were associated with intrinsic apoptosis pathway and disrupted NF-κB signaling. These results suggested that xanthatin may have therapeutic potential against NSCLC.

【 授权许可】

CC BY   
© 2012 by the authors; licensee MDPI, Basel, Switzerland.