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Article Publish Status: FREE
Abstract Title:

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

Abstract Source:

Sci Rep. 2015 Dec 17 ;5:18457. Epub 2015 Dec 17. PMID: 26672742

Abstract Author(s):

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

Article Affiliation:

Rakesh K Arya

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

Study Type : Animal Study, In Vitro Study

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Sayer Ji
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