Medicinal Chemistry

Angio Suppressive Effect of Clitoria ternatea Flower Extract is Mediated by HIF-1α and Down Regulation of VEGF in Murine Carcinoma Model

Abstract

Kaythegowdanadoddi Srinivasa Balaji, Priyanka Shivaprakash, Saligrama Devegowda Preethi, Kagepura Thammaiah Chandrashekara, Lokesh Siddalingaiah, Kanchugarakoppal Subbegowda Rangappa and Shankar Jayarama

Angiogenesis is a vital process in the progression of cancer as it also play a key role in tumor transition from its dormant state to a malignant stage. VEGF is key growth factor plays an important role in angiogenesis and is regulated by transcription factor HIF-1α. Natural compounds derived from plants have been a prime source for numerous clinically useful anti-cancer agents specially for targeting neo-angiogenesis. Medicinal plants continue to play a central role in the healthcare system of large proportions of the world’s population, particularly true in developing countries like India. In the current report, we studied the angio suppressive
effect of aqueous extract of Clitoria ternatea in EAC cells induced angiogenesis. In vivo anti-angiogenic effect of C. ternatea was demonstrated by the down regulation of VEGF secretion from Ehrlich ascites carcinoma (EAC) cells and inhibition of blood vessels formation indicating the potential angio suppressive effect of plant. HIF-1α protein, a transcription factor known to be key a regulator in hypoxia-induced angiogenesis was also down regulated by C. ternatea. Our invetigation indicated that, HIF-1α nuclear sequestration is repressed by C. ternatea through inhibition of nuclear translocation. We hypothesize that decreased levels of HIF-1α in the nucleus of EAC cells upon MECT treatment could be responsible for decreased expression of VEGF which is also attributed to the angio-suppressive effects of MECB. C. ternatea promises to be a potential anti-angiogenic plant which can be exploited to treat cancer.