Anti-breast tumor activity of Eclipta extract in-vitro and in-vivo: novel evidence of endoplasmic reticulum specific localization of Hsp60 during apoptosis

• DOI: 10.1038/srep18457
• Publication Date: 2015-12-17T10:10:12Z
• Authors: Rakesh K. Arya; Akhilesh Singh; Navneet K. Yadav; Srikanth H. Cheruvu; Zakir Hossain; Sanjeev Meena; Shrankhla Maheshwari; Anup K. Singh; Uzma Shahab; Chetan Sharma; Kavita Singh; Tadigoppula Narender; Kalyan Mitra; Kamal R. Arya; Rama K. Singh; Jiaur R. Gayen; Dipak Datta
• Keywords: HSP60

Abstract Major challenges for current therapeutic strategies against breast cancer are associated with drug-induced toxicities. Considering the immense potential of bioactive phytochemicals to deliver non-toxic, efficient anti-cancer therapeutics, we performed bio-guided fractionation Eclipta alba extract and discovered that particularly chloroform fraction (CFEA) is selectively inducing cytotoxicity cells over non-tumorigenic epithelial cells. Our unbiased mechanistic hunt revealed CFEA specifically activates intrinsic apoptotic pathway by disrupting mitochondrial membrane potential, upregulating Hsp60 downregulating expression anti-apoptotic protein XIAP. By utilizing specific siRNA, identified a novel pro-apoptotic role uncovered following treatment, upregulated localized in endoplasmic reticulum (ER). To our knowledge, this first evidence ER localization during cell apoptosis. Further, LC-MS approach luteolin mainly attributed its activities. Moreover, oral administration not only offers anti-breast effects in-vivo but also mitigates tumor induced hepato-renal toxicity. Together, studies offer insight into mediated inhibition may potentially open up new avenues further translational research.