Arctigenin enhances chemosensitivity of cancer cells to cisplatin through inhibition of the STAT3 signaling pathway
Article first published online: 19 SEP 2011
Copyright © 2011 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 112, Issue 10, pages 2837–2849, October 2011
How to Cite
Yao, X., Zhu, F., Zhao, Z., Liu, C., Luo, L. and Yin, Z. (2011), Arctigenin enhances chemosensitivity of cancer cells to cisplatin through inhibition of the STAT3 signaling pathway. J. Cell. Biochem., 112: 2837–2849. doi: 10.1002/jcb.23198
- Issue published online: 19 SEP 2011
- Article first published online: 19 SEP 2011
- Accepted manuscript online: 23 MAY 2011 08:14AM EST
- Manuscript Accepted: 14 MAY 2011
- Manuscript Received: 14 JAN 2011
- The National Natural Science Foundation of China. Grant Numbers: 81072433, 31071000
Arctigenin is a dibenzylbutyrolactone lignan isolated from Bardanae fructus, Arctium lappa L, Saussureamedusa, Torreya nucifera, and Ipomea cairica. It has been reported to exhibit anti-inflammatory activities, which is mainly mediated through its inhibitory effect on nuclear transcription factor-kappaB (NF-κB). But the role of arctigenin in JAK-STAT3 signaling pathways is still unclear. In present study, we investigated the effect of arctigenin on signal transducer and activator of transcription 3 (STAT3) pathway and evaluated whether suppression of STAT3 activity by arctigenin could sensitize cancer cells to a chemotherapeutic drug cisplatin. Our results show that arctigenin significantly suppressed both constitutively activated and IL-6-induced STAT3 phosphorylation and subsequent nuclear translocation in cancer cells. Inhibition of STAT3 tyrosine phosphorylation was found to be achieved through suppression of Src, JAK1, and JAK2, while suppression of STAT3 serine phosphorylation was mediated by inhibition of ERK activation. Pervanadate reversed the arctigenin-induced downregulation of STAT3 activation, suggesting the involvement of a protein tyrosine phosphatase. Indeed, arctigenin can obviously induce the expression of the PTP SHP-2. Furthermore, the constitutive activation level of STAT3 was found to be correlated to the resistance of cancer cells to cisplatin-induced apoptosis. Arctigenin dramatically promoted cisplatin-induced cell death in cancer cells, indicating that arctigenin enhanced the sensitivity of cancer cells to cisplatin mainly via STAT3 suppression. These observations suggest a novel anticancer function of arctigenin and a potential therapeutic strategy of using arctigenin in combination with chemotherapeutic agents for cancer treatment. J. Cell. Biochem. 112: 2837–2849, 2011. © 2011 Wiley-Liss, Inc.