Synergistic activity for natural and synthetic inhibitors of angiogenesis induced by murine sarcoma L-1 and human kidney cancer cells

Abstract

Tumor angiogenesis is an important link in the process of tumor growth and metastasis. A number of substances with an anti-angiogenic activity has been described, but their efficiency remains low. Many researchers believe that a better therapeutic effect could be achieved using a cocktail of several anti-angiogenic agents, having different points of action. A lot of synthetic and natural products of plant and animal origin have anti-tumor and anti-angiogenic properties. The aim of the present study was to evaluate the effect of some combinations of angiogenesis inhibitors on the growth and neovascularization of murine sarcoma L-1, and on angiogenesis induced in the mouse skin by grafting of human renal cancer. The influence of theobromine, sulindac and its metabolite sulindac sulfone, chlorogenic acid, and shark liver oil on the afferent and efferent angiogenesis pathways was tested. Individually, all of these substances suppressed tumor growth and angiogenesis. Synergy was found for a combination of theobromine, sulindac, and chlorogenic acid (L-1 sarcoma tumor growth), and for theobromine with sulindac sulfone or with shark liver oil, which were given to the mice grafted with human renal cancer cells (angiogenesis). No synergistic effects were shown after preincubation with tumor cells and inhibitors.