Inhibition of Angiogenesis and Metastasis by Cheilanthes farinosa (Forsk.) Kaulf water extract

Summary. Cheilanthes farinosa (Forsk.) Kaulf has been used by the Gaddis Tribe of Himachal Pradesh to treat diseases that simulate the symptoms of jaundice, a pathological condition of hepatic damage. The current study aimed to validate this traditional knowledge scientifically by evaluating the anti-angiogenic, anti-metastatic and anti-invasive properties of the water extract of this plant using in ovo , in vitro as well as gene expression level studies. Chorio-Allantoic Membrane (CAM) assay proved the ability of the extract in inhibiting vascular development. The expression of Vascular Endothelial Growth Factor (VEGF) was significantly lowered by the action of the extract. The results of the wound scrap assay and cell invasion assay in Hep3B hepatocellular carcinoma cells suggest the anti-migratory effects of the extract. Cell cycle arrest induced by the extract was also evaluated. Preliminary qualitative phytochemical analysis of the extract revealed the presence of saponins, phenolic compounds, and flavones. High Performance Liquid Chromatography (HPLC) analysis confirmed the presence of Chlorogenic acid, Caffeic acid and Rutin in trace concentrations. All these findings point towards the prospects of C. farinosa and its bioactive components to be developed as an effective treatment for Hepatocellular carcinoma, it being a highly vascularized tumor. Industrial relevance. Angiogenesis plays a pivotal role in controlling many diseases and drugs with angiogenic effects are looked up on for treating cancer, diabetic retinopathy, ulcer and so on. Cheilanthes farinosa , a fern, is used by traditional healers and tribal people for treating ailments of liver. It was then experimentally proved to be effective for selectively destroying hepatic cancer cell line, grown in vitro . Hepatic cancer is neovascularised tumor and anti-angiogenic therapy will be an effective mode of therapy. Furthermore, cancer is a multifactorial disease and different modes of treatment are required to suppress it. The apoptotic effect of water extract of C. farinosa in hepatic cancer cells has already been reported. Many plant derived drugs have not been industrially successful due to the inability to mass produce the plants, to meet the bulk requirement. Moreover, the plant may be endemic to forest area and the anthropic pressure may destroy its natural habit and thereby hindering its growth. C. farinosa is grown luxuriantly in hilly areas and needs little attention. These factors make it useful industrial raw material to develop a pharmaceutical product.  Therefore, it will be industrially relevant to develop a plant derived drug that has multiple action against hepatic cancer and thus evaluated the antiangiogenic effect of Cheilanthes farinosa. Keywords. Cheilanthes farinose ; anti-angiogenesis; anti-migratory; cell invasion; HPLC