ANTI-ANGIOGENIC ACTIVITY OF ANNONA RETICULATA N-HEXANE SEEDS EXTRACT : IN VIVO STUDY.

Angiogenesis is the physiological process through which new blood vessels generate from pre-existing vessels and it acquired therapeutic value in cancer treatment because malignant tissue required the formation of new blood vessels to grow and metastasize. Bevacizumab is a recombinant humanized monoclonal antibody. It is the first angiogeneic inhibitors used clinically. There are number of resistance mechanisms and some serious adverse effects associated with its usage. Recently, there are many studies about the anticancer activity of various extracts of Annona reticulata and their major active constituent’s acetogenins (AGEs) against different cancer cell lines. However, to our knowledge, the antiangiogenic effect of A. reticultata is not verified till now. This study aimed to examine A. reticualta n-hexane seed extract antiangiogenic activity in in vivo study. The determination of LD₅₀ done by Karber method, then in vivo study was done, n –hexane seeds extract was tested against mammary adenocarcinoma AM3 transplanted in mice. In vivo results showed significant reduction in relative tumor volume (RTV) and tumor growth inhibition percentage (TGI%) and the formation of blood vessels of tumor mass in treated groups. Microarray analysis of 24 different angiogenesis factors revealed that n-hexane extract down-regulated number of proangigeneic factors like (TNF-α, IL-β, MCP and VEGF-A). Chemical analysis of the extract were done by Gas chromatography-mass spectrometry (GC-MS) analysis, which revealed the presence of acetogenin compounds in extract. The study suggested that n-hexane seeds extract of A. reticulata can suppress angiogenesis by interfering with angiogenic factors that might reduce tumor growth and metastasis. [ABSTRACT FROM AUTHOR]