2-(1-Hydroxethyl)-4,8-dihydrobenzo[1,2-b:5,4-b′]dithiophene-4,8-dione (BTP-11) enhances the ATRA-induced differentiation in human leukemia HL-60 cells

Received 20 January 2009; received in revised form 13 February 2009; accepted 15 February 2009.

Abstract

2-(1-Hydroxethyl)-4,8-dihydrobenzo[1,2-b:5,4-b′]dithiophene-4,8-dione (BTP-11) is a potent enhancer for all-trans retinoic acid (ATRA)-induced differentiation in HL-60 cells. Combination of BTP-11 and ATRA cut down the concentration of ATRA significantly, and that BTP-11 promoted the progression of ATRA-induced into the terminal granulocytic differentiation. Further, Western blot analysis revealed that combination of BTP-11 and ATRA decreased cyclin D/CDK4 and increased C/EBPɛ protein expression to arrest the cells into G0/G1 phase leading to granulocytic maturation. These results confirmed that BTP-11 is a potent enhancer for ATRA-induced differentiation of HL-60 cells, and the great developmental potential of BTP-11 will be expected.

Keywords: ATRA, CDK1, C/EBPɛ, Cyclin D, Differentiation, G0/G1 phase arrest, HL-60, 2-(1-Hydroxethyl)-4,8-dihydrobenzo[1,2-b:5,4-b′]dithiophene-4,8-dione (BTP-11)

a Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung, Taiwan

b Pharmaceutical Technology Division, Biomedical Engineering Center, Industrial Technology Research Institute, Hsinchu, Taiwan

c Natural Products Research Laboratories, School of Pharmacy, University of North Carolina, USA

Corresponding author. Tel.: +886 4 22030760; fax: +886 4 22030760.

PII: S0145-2126(09)00099-X

doi:10.1016/j.leukres.2009.02.023

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