Rothman, Deborah, Gao, Xiaolin, George, Elizabeth, Rasmusson, Timothy, Bhatia, Diksha, Alimov, Irina, Wang, Louis, Kamel, Amin, Hatsis, Panagiotis, Tutter, Antonin, Feng, Yan, Michaud, Gregory, Mcdonald Iii, Earl, Venkatesan, Kavitha, Farley, David, Digan, Mary, Ni, Yucheng, Harbinski, Fred, Gunduz, Mithat, Colizza, Kevin, Wilson, Chris, Buckler, Alan, Labow, Mark, Tallarico, John, Myer, Vic, Porter, Jeffrey and Wang, Shaowen (2015) SULT1A: the trigger for N-Benzyl Indole Carbinol tumor growth suppression. SULT1A1: the trigger for N-Benzyl Indole Carbinol tumor growth suppression, 22 (9). pp. 1228-1237. ISSN 1879-1301

Abstract

Through a multi-faceted approach, we have identified a compound series, N-Benzyl Indole Carbinols (N-BICs), which selectively kills cancer cells expressing high levels of the phase II metabolic enzyme sulfotransferase 1A1 (SULT1A1). Compounds were identified via screening for molecules which could selectively kill cancer cells of differing p53 status. To better understand the features which render cells sensitive to the N-BICs, cell line profiling and computational analysis revealed SULT1A1 as a distinguishing feature.
Further, we understand that SULT1A1 activates the N-BICs by rendering the compounds strong electrophiles which can alkylate multiple proteins in the cell and induce cell death. N-BICs are synthetic analogs of the natural product indole-3-carbinol (I3C) found in cruciferous vegetables. I3C has been reported in the literature to be anti-proliferative in cancer cells. Herein we demonstrate the selectivity profile for N-BICs is through activation by SULT1A1 to induce cell death effects.

Item Type:	Article
Keywords:	Tumor supression, N-BICs, SULT1A1, covalent modifier
Date Deposited:	26 Apr 2016 23:46
Last Modified:	26 Apr 2016 23:46
URI:	https://oak.novartis.com/id/eprint/21295