Plumbagin triggers DNA damage response, telomere dysfunction and genome instability of human 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, were evaluated in breast cancer cells. To evaluate the effects of plumbagin on breast cancer cell types, we employed a variety of techniques comprising cell viability, cell cycle assay, comet assay, western blotting, immunocytochemistry, measurement of telomerase activity, telomere restriction fragment length, quantitative fluorescence in situ hybridisation, along with gene expression analysis of untreated cells. Plumbagin treatment induced cytotoxicity in human breast cancer cells along with cell cycle arrest, DNA damage and cell death leading to apoptosis. Plumbagin was also found to suppress the telomerase activity in cancer cells accompanied by telomere attrition. Telomere shortening was corroborated by reduced telomere fluorescence on chromosome ends and genome instability. Together, these findings may suggest the application of plumbagin as adjuvant modality in breast cancer therapeutics.