
In this study, we examined the inhibitory effect of bee venom (BV) and its major peptides, melittin and apamin, on PMA-induced invasion induced by MMP-9 expression in Caki-1 renal cancer cells.
BV and melittin, but not apamin, significantly suppressed PMA-induced invasion by inhibiting MMP-9 expression in Caki-1 cells. Furthermore, as evidenced by MMP-9 promoter assays, melittin inhibited MMP-9 gene expression by blocking the PMA-stimulated activations of activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappaB).
In addition, melittin suppressed the PMA-induced phosphorylations of ERK and JNK mitogenactivated protein kinases, upstream factors involved in Ap-1 and NF-kappaB.
These results suggest that the suppression of MMP-9 expression contributes to the anti-tumor properties of melittin.
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