CAPSAICIN INHIBITS TNF-α-INDUCED MIGRATION AND MMP-9 ACTIVITY IN LUNG CANCER CELLS THROUGH ERK, P38 AND AP-1 SIGNALING PATHWAY

Tran Thi Hien^1,2*, Dao Trong Tuan^3,4, Do Thi Ha³, Nguyen Minh Khoi³

³Vietnam National Institute of Medicinal Materials; ⁴University of Copenhagen, Denmark; ¹Thaibinh Medical University; ²Faculty of medicine, Lund University, Sweden

*Corresponding author: Thi.Hien_Tran@med.lu.se

(Received August 20^th, 2014)

Summary

Capsaicin Inhibits TNF-α-Induced Migration and MMP-9 Activity in Lung Cancer Cells through ERK, P38

and AP-1 Signaling Pathway

Capsaicin, an alkaloid of the plant kingdom restricted to the genus Capsicum, has shown chemopreventive properties against certain carcinogens and mutagens, and also exerts anticancer activity. Here, we demonstrated the anti-migration activity of capsaicin in lung cancer cell line A549. Capsaicin dose-dependently reduced TNF-α-stimulated matrix metalloproteinases-9 (MMP-9) activation and therefore inhibited A549 cell migration. Additionally, capsaicin suppressed TNF-α-stimulated expression of MMP-9 protein, mRNA and transcription activity levels. Furthermore, as the evidenced by MMP-9 promoter and electrophoretic mobility assays, capsaicin significantly inhibited the TNF-α-stimulated phosphorylation of ERK and p38, upstream factors involved in AP-1 activation, whereas the TNF-α-stimulated phosphorylation of PI3K/AKT and JNK was not affected by capsaicin. Hence, our results suggested that the inhibitory effect of capsaicin on MMP-9 activation, which is closely related to tumor migration, possibly involves mechanisms of its ability to suppress TNF-α-stimulated AP-1 activation through inhibition of ERK, p38 signaling pathway. Overall, capsaicin may be a valuable anti-invasive drug candidate for cancer therapy.

Keywords: Capsaicin, MMP-9, A549.

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