Abstract: 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 IκBa, which might also contribute to its pro-apoptotic effects on A549 cells. Xanthatin also inhibited TNFa 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.
Keywords: xanthatin; non-small-cell lung cancer; cytotoxicity; cell cycle; apoptosis
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Zhang, L.; Ruan, J.; Yan, L.; Li, W.; Wu, Y.; Tao, L.; Zhang, F.; Zheng, S.; Wang, A.; Lu, Y. 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 2012, 17, 3736-3750.
Zhang L, Ruan J, Yan L, Li W, Wu Y, Tao L, Zhang F, Zheng S, Wang A, Lu Y. 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. 2012; 17(4):3736-3750.
Zhang, Lei; Ruan, Junshan; Yan, Linggeng; Li, Weidong; Wu, Yu; Tao, Li; Zhang, Feng; Zheng, Shizhong; Wang, Aiyun; Lu, Yin. 2012. "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 17, no. 4: 3736-3750.