Cell-Type-Specific Effects of Silibinin on Vitamin D-Induced Differentiation of Acute Myeloid Leukemia Cells Are Associated with Differential Modulation of RXRα Levels.pdfVIP

Hindawi Publishing Corporation Leukemia Research and Treatment Volume 2012, Article ID 401784, 12 pages doi:10.1155/2012/401784 Research Article Cell-Type-Specific Effects of Silibinin on Vitamin D-Induced Differentiation of Acute Myeloid Leukemia Cells Are Associated with Differential Modulation of RXRα Levels Rina Wassermann, Victoria Novik, and Michael Danilenko Department of Clinical Biochemistry, Faculty of Health Sciences, Ben-Gurion University of the Negev, P.O. Box 653, 84105 Beer-Sheva, Israel Correspondence should be addressed to Michael Danilenko, misha@bgu.ac.il Received 26 February 2012; Accepted 15 March 2012 Academic Editor: George P. Studzinski Copyright © 2012 Rina Wassermann et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Plant polyphenols have been shown to enhance the differentiation of acute myeloid leukemia (AML) cells induced by the hormonal form of vitamin D (1α,25-dihydroxyvitamin D ; 1,25D). However, how these agents modulate 1,25D effects in different subtypes 3 3 of AML cells remains poorly understood. Here, we show that both carnosic acid (CA) and silibinin (SIL) synergistically enhancd 1,25D-induced differentiation of myeloblastic HL60 cells. However, in promonocytic U937 cells, only CA caused potentiation while SIL attenuated 1,25D effect. The enhanced effect of 1,25D+CA was accompanied by increases in both the vitamin D receptor (VDR) and retinoid X receptor alpha (RXRα) protein levels and vitamin D response element (VDRE) transactivation in both cell lines. Similar increases were observed in HL60 cells treat