ANTI-CANCER EFFECTS, MECHANISM OF ACTION AND COMBINATION THERAPEUTICS OF PLUMBAGIN, A NATURAL PLANT PRODUCT, IN BREAST CANCER CELLS

Abstract

Natural plant products are increasingly being used in cancer therapeutic studies due to their reduced normal cell toxicity. In this study, the anti-cancer properties of Plumbagin, a naphthoquinone derivative extracted from the roots of Plumbago, was evaluated in breast cancer cells. It was shown that Plumbagin induces specific cytotoxicity in human breast cancer cells along with DNA damage, telomere attrition and cell death leading to apoptosis. Through a microarray-based study, the molecular mechanism of action of this plant chemical was also investigated, showing that Plumbagin dysregulates multiple cancer-related pathways at genetic level and plays a crucial role in suppressing breast cancer cell proliferation, survival, telomere dynamics, invasion and metastasis. In the other part of this study, based on the kinetic investigations of Plumbagin, three signaling pathway specific inhibitors were selected to explore their combinatory effects along with Plumbagin treatment. It is proposed that application of Plumbagin, in both single and combination studies may suggest promising targeted therapeutics in breast cancer treatment modalities.