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

• Published in: Regulatory toxicology and pharmacology 2018-06, Vol.95, p.400-411
• Main Authors: Sakthivel, Kunnathur Murugesan, Guruvayoorappan, Chandrasekaran
• Format: Article
• Language: English
• Subjects: Acacia ferruginea; Angiogenesis; B16F-10 melanoma cells; Cytokines; Metastasis
• ISSN: 0273-2300; 1096-0295
• DOI: 10.1016/j.yrtph.2018.04.012

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. [Display omitted] •Administration of AFE shown reduced metastatic colony formation in lungs and prolonged survival in tumor-bearing hosts.•AFE administration shown significant reduction in number of tumor directed capillaries by regulating cytokines and VEGF.•AFE could be a promising candidate for developing anti-cancer agents targeting metastasis and angiogenesis.