Targeted inhibition of tumor survival, metastasis and angiogenesis by Acacia ferruginea mediated regulation of VEGF, inflammatory mediators, cytokine profile and inhibition of transcription factor activation

Abstract

Acacia ferruginea extract (AFE) was studied for anti-metastasis/-angiogenesis activity against B16F-10 melanoma cells in C57BL/6 mice. In vitro cytotoxicity of AFE was first screened using MTT assay and it was shown to inhibit B16F-10 cells with IC50 value of 52.94 μg/ml. Anti-metastatic activity of AFE in vivo revealed administration of AFE (10 mg/kg.b.wt) in three different regimens has shown reduced metastatic colony formation in lungs and prolonged survival in metastatic tumor-bearing hosts. Biochemical analysis shown that treatment with AFE significantly reduced the lung collagen hydroxyproline, hexosamine, uronic acid, sialic acid and gamma-glutamyl transpeptidase content. Administration of AFE significantly inhibited the iNOS and COX-2 level, diminished the infiltration of neoplastic cells and subsequently reduced the number of p53 and Bcl-2 positive immunoreactive cells as evidenced by histological and immunohistochemistry analysis. In addition, we found that, AFE significantly decreased the level of pro-inflammatory cytokines interleukin-1β, IL-6, TNF-α and suppressed the nuclear factor kappa B (NF-κB) activation. Furthermore, angiogenesis studies shown significant reduction in number of tumor directed capillaries, regulating cytokines and vascular endothelial growth factor (VEGF). Our present results suggests that AFE could be a promising candidate for developing anti-cancer agents targeting metastasis which helps further to combat melanoma with effective treatment strategy.