Valproic acid (VPA) as a broad-spectrum inhibitor of
histone deacetylase, has been used in
cancer therapy. Recently, the combination of VPA with other
anticancer agents has been considered as a useful and necessary strategy to inhibit
tumor growth and progression. The
coumarin derivates from natural plants have been shown to be the promising natural
anticancer agents. However, no literature is available on the anticancer effects of the combination of VPA and
coumarin-3-carboxylic acid (HCCA). Here we show that this combination significantly increases inhibitory effects against the proliferation and migration in highly-metastatic
lung cancer cells by inducing apoptosis and cell cycle arrest as well as regulating related
protein expressions. Our results indicate that this combination of VPA with HCCA not only enhances the
protein levels of Bax, cytosolic
cytochrome c,
caspase-3 and PARP-1 but also reduces the
protein expressions of Bcl-2,
cyclin D1 and NF-κB as well as inhibits the phosphorylation and expressions of Akt, EGFR, VEGFR2 and c-Met in the
cancer cells. Our results suggest that the combination of VPA with HCCA suppresses the proliferation and migration of
lung cancer cells via EGFR/VEGFR2/c-Met-Akt-NF-κB signaling pathways; this combination may have a wide therapeutic and/or adjuvant therapeutic application in the treatment of
lung cancer.