Ajithkumar, GS and Vinitha , A and Binil Raj , SS and CC, Kartha (2016) Drug Resistance of Endocardial Endothelial Cells is Related to Higher Endogenous ABCG2. Cardiovascular toxicology, 16 (4). pp. 390-405. ISSN 1559-0259

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Abstract

Endocardial endothelial cells (EECs), when compared with endothelial cells of arteries and veins, possess higher resistance to apoptosis-inducing anticancer agents. The mechanism of this resistance property is unknown. We have investigated the molecular mechanism, which contributes to increased cell survival capacity in EECs. We explored whether the resistance to apoptosis is associated with the cellular expression of ATP-binding cassette transporters such as P-glycoprotein, MRP-1, and ABCG2. We used primary and immortalized porcine endocardial endothelial cells (PEECs and hTERT PEECs) and compared the results with that in porcine aortic endothelial cells (PAECs), left atrioventricular valve endothelial cells (PVECs), and human umbilical vein endothelial cell line (EA.hy926). FACS and immunoblot analysis revealed a significantly higher expression of ABCG2 in PEECs and hTERT PEECs compared to PAECs, PVECs, and EA.hy926. Using apoptosis-inducing anticancer agents such as doxorubicin and camptothecin, through chromatin condensation assay and immunoblot analysis, we demonstrated a higher resistance to apoptosis in EECs compared to PAECs, PVECs, and EA.hy926. Interestingly, resistance in EECs reversed in presence of ABCG2 specific inhibitor, fumitremorgin C. Our observations suggest that an inherently high expression of ABCG2 in EECs protects them against apoptosis in presence of anticancer agents.

Item Type:	Article
Uncontrolled Keywords:	Endocardial endothelial cells ABCG2 Apoptosis Doxorubicin Camptothecin Fumitremorgin C Pheophorbide-A
Subjects:	Cardiovascular Diseases And Diabetes Biology
Depositing User:	Central Library RGCB
Date Deposited:	24 Mar 2017 05:49
Last Modified:	24 Mar 2017 05:49
URI:	http://rgcb.sciencecentral.in/id/eprint/317

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