Scutellarein antagonizes the tumorigenesis by modulating cytokine VEGF mediated neoangiogenesis and DFF-40 actuated nucleosomal degradation

• Published in: Biochemical and biophysical research communications 2017-02, Vol.484 (1), p.85-92
• Main Authors: Thirusangu, Prabhu, Vigneshwaran, V., Vijay Avin, B.R., Rakesh, H., Vikas, H.M., Prabhakar, B.T.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; Antiangiogenesis; Apigenin - pharmacology; Apoptosis; Cancer; Carcinogenesis - drug effects; Cell Line, Tumor; Cell Proliferation - drug effects; Deoxyribonucleases - pharmacology; Humans; IN VIVO; Mice; Mice, Inbred BALB C; Neovascularization, Pathologic - chemically induced; NUCLEAR FRAGMENTATION; Nucleosomes - metabolism; OXIDATION; Oxidative stress; Rats; Scutellarein; STRESSES; Vascular Endothelial Growth Factor A - physiology
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.01.067

Neoplastic cells often reside in distinctive tumor hypoxia armed with a series of adaptive responses including oxidative stress, defective apoptotic machinery and neoangiogenesis, through that further confer cell survival improvement. Plants still acts as reservoir of natural chemicals to provide newer active pharmacophores. Scutellarein is flavones which has wide range of pharmacophoral effects. In our current research, scutellarein employed for targeting oxidative stress mediated tumor angiogenesis and apoptotic nuclear fragmentation. Experimental results revealed that scutellarein has antiproliferative index against multiple cancer cell lines and diminished the oxidative stress and tumor development of murine ascitic lymphoma & inflammatory hepatocellular carcinoma. Eventual consequences lead to reduced neovessel formation by abrogating angiogeneic factors cytokine-VEGF-A, Flt-1, HIF-1α, MMP-2 and MMP-9 and reversing of evading apoptosis by activating caspase-3 activated DNA fragmentation factor (DFF-40) mediated nucleosomal degradation. In summary, our experimental evidences suggest that scutellarein has strong potentiality to attenuate the tumor development by modulating sprouting neovasculature and DFF-40 mediated apoptosis. •Scutellarein exhibits potent neoplastic effect against ascitic and DEN-induced liver carcinoma in-vivo.•Scutellarein reticence the oxidative stress and angiogenesis on tumor and non-tumor models.•Scutellarein modulates tumor vasculature by altering tumor angiogenic factor’s expressions.•Scutellarein actuates the DFF-40 mediated nucleosomal degradation in DLA tumor.