Determining the cytotoxic properties of a Fagonia indica extract on breast and colon cancer

Abstract

Fagonia indica is an herbaceous plant common to dry arid environments, including those across Eastern Europe and the Middle East. Traditional communities; particularly those in small villages of Pakistan, utilise Fagonia indica as an alternative medicine for a number of ailments, including breast cancer. Previous research has demonstrated several lines of antineoplastic activity from an aqueous extract of Fagonia indica against breast cancer cell lines, in vitro. Cytotoxicity in these cell lines was associated with activation of p53 and FOXO3a which were able to inhibit cell cycle progression and induce apoptosis in breast cancer. Despite this, there is still a limited understanding on the breadth of effects of Fagonia indica treatment, particularly against other aspects of tumorigenesis. The present study aimed to determine the mechanisms of action of an aqueous extract of Fagonia indica against phenotypically distinct breast and colon cancer cell lines. One of the most confounding issues in cancer treatment, is the acquisition of resistance mechanisms against commonly used chemotherapies. For the first time, this study also investigated the effect of Fagonia indica treatment against multi-drug resistant breast and colon cancer cell lines. An aqueous extract of Fagonia indica was able to induce cell death in wild-type and chemotherapy resistant breast and colon cancer cell lines, in correlation with a dysregulation of metabolism/ ATP production. Other associated mechanisms of action of Fagonia indica included down-regulation of VEGF, ICAM-1 and NF-kB expression, related to angiogenic and inflammatory processes. The effect of Fagonia indica on chemotherapy resistant breast and colon cancer cell lines was associated with down-regulation of ABC transporters; ABCC4 and AGCG2. Investigation into the chemical properties of Fagonia indica revealed that a methanolic extract of Fagonia indica had increased total flavonoid, triterpene and antioxidant contents which was associated with increased antineoplastic activity in vitro. Further work is required to separate and identify individual compounds from this methanolic fraction for development into a therapeutic treatment.