Antiangiogenic and Proapoptotic Activity of Averrhoa Carambola L. Fruit Extract on Ehrlich Ascites Carcinoma Treated Mice.

ABSTRACT

Aim: Accumulation of fluid containing cancer cells in the abdomen particularly, in ovarian cancer, forms malignant ascites rendering poor prognosis at this stage. We investigated the tumor inhibitory activity of Averrhoa carambola L. fruit extract on EAC cells administered mice targeting angiogenesis and apoptosis, and the bioactive compounds responsible. Main Methods: Body weight, ascites volume and peritoneal angiogenesis were monitored. Giemsa staining on EAC cells, DNA fragmentation assay and FACS analysis to determine the growth arrest were conducted. VEGF count was monitored using ELISA. Phytochemical screening and HPLC analysis were conducted to determine the bioactive compounds. Key Findings: The fruit extract expressed direct cytotoxicity to EAC cells by inducing apoptosis as evidenced by decrease in tumor volume, viable cell count and body weight of EAC bearing mice; characteristic apoptotical features, DNA fragmentation of apoptosis, and growth arrest taking place at G2/M phase of the cell cycle. Significant decrease in density of microvessel network in peritoneal lining and VEGF count in treated cells indicated that the fruit extract curbed malignancy of tumor through its antiangiogenic activity also. All these can be attributed to catechin, epicatechin and ferulic acid present in the extract. The total phenolic, flavanoids, proancthocyanidin and condensed tannins content were 1.216 mgGAE/g extract, 767 mgCE/g extract, 586 mgCE/ g extract and 18.35 mgCE/g extract respectively. Significance: The present study is the first to provide direct evidence that Averrhoa carambola L. has potent proapoptotic and antiangiogenic activity which may contribute to its well- documented clinical activity as a pharmaceutical drug.