Anti-angiogenic activity from the fruit latex of Ficus carica (Fig)

The common fig, Ficus carica L. (Moraceae), is an important economic plant for its use as a food, but it also has a long history of use as a medicinal plant. Both ancient and more recent herbal texts mention the use of figs for treatment of a number of ailments including malignant ulcers, sores, swellings, and also as a useful therapy for chronic illnesses. In the early 1950's a physican, Dr. Solomon Ullman, reported promising anticancer activity of a F. carica extract in mice and dogs. The long historical medicinal use together with these preliminary animal studies prompted us to investigate the possible anticancer potential of figs. Angiogenesis, a complex multi-step process resulting in the formation of new blood vessels, is required for the growth and spread of tumor cells. Inhibition of tumor angiogenesis is therefore considered a promising anticancer target. Latex from immature fruits of several different F. carica varieties were tested for anti-angiogenic activity in a unique system involving the use of segments of placental veins and human tumor biopsies. Three out of six of these varieties demonstrated significant anti-angiogenic activity, yet were non-toxic. This non-toxic, anti-angiogenic activity was confirmed using a human umbilical vein endothelial cell (HUVEC) tubule formation assay and a MTT antiproliferation assay. The F. carica variety with the most promising biological activity was chosen for additional evaluation. In HUVEC cells, there was a marked concentration-dependent decrease in both the content of vascular endothelial growth factor (VEGF), a major pro-angiogenic growth factor involved in the angiogenesis process, as well as downregulation of VEGF receptor. There was, however, no effect on secretion of basic fibroblast growth factor (bFGF), another pro-angiogenic growth factor. The fig extract has undergone preliminary chemical characterization using LC-MS/MS and rutin was found to be a major constituent. Acknowledgements: Ullman Medical, Inc. and The Beverage Institute for Health and Wellness. References: 1. Lansky EP, Paavilainen H. et al. (2008), J. Ethnopharmacol., in press.