Herbacetin suppressed MMP9 mediated angiogenesis of malignant melanoma through blocking EGFR-ERK/AKT signaling pathway

Abstract

Malignant melanoma remains a challenge for clinical practice and novel therapeutic strategies are urgently needed. Herbacetin, a natural flavonoid compound that has multiple pharmacological activities, exerts anticancer effects on several human tumors. In this study, the anti-angiogenesis effect of Herbacetin in human malignant melanoma was investigated. The results indicated that Herbacetin treatment significantly suppressed tumor growth and angiogenesis of malignant melanoma both in vitro and in vivo. In melanoma A375 and Hs294T cells, Herbacetin treatment suppressed both EGF-induced and constitutive phosphorylation of EGFR, accelerated the internalization and degradation of EGFR, and subsequently suppressed the activation of the downstream kinases (AKT and ERK). Moreover, MMP9 was determined as a key angiogenic factor in Herbacetin treated melanoma cells. Knockdown of MMP9 suppressed the in vitro angiogenesis while overexpression of MMP9 in Herbacetin treated melanoma cells restored the angiogenesis ability. We concluded that Herbacetin suppressed melanoma angiogenesis through blocking EGFR-ERK/AKT-MMP9 signaling pathway and Herbacetin may be developed as a potential drug for melanoma treatment.