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Molecules 2012, 17(4), 3736-3750; doi:10.3390/molecules17043736
Article

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

1,2,†, 1,†, 1, 1, 1, 1, 1, 1,3, 1,3 and 1,3,*
Received: 14 February 2012; in revised form: 13 March 2012 / Accepted: 20 March 2012 / Published: 26 March 2012
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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 xanthatin; non-small-cell lung cancer; cytotoxicity; cell cycle; apoptosis
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

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.

Chicago/Turabian Style

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.



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