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Toxicological Research 2008-Mar

The Effects of Crinum asiaticum on the Apoptosis Induction and the Reversal of Multidrug Resistance in HL-60/MX2.

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Jae-Hee Hyun
Jung-Il Kang
Sang-Cheol Kim
Elvira Kim
Ji-Hoon Kang
Jung-Mi Kwon
Doek-Bae Park
Young-Jae Lee
Eun-Sook Yoo
Hee-Kyoung Kang

Keywords

Abstract

The present study investigated the anti-proliferative and chemosensitizing effects of Crinum asiaticum var. japonicum against multi-drug resistant (MDR) cancer cells. The 80% methanol extract, chloroform (CHCI3) fraction and butanol (BuOH) fraction of C asiaticum inhibited the growth of mitoxantrone (MX) resistant HL-60 (HL-60/MX2) cells. When HL-60/MX2 cells were treated with the CHCI3 and BuOH fractions, DNA ladder and sub-G1 hypodiploid cells were observed. Furthermore, the fractions reduced Bcl-2 mRNA levels, whereas Bax mRNA levels were increased. These results suggest that the inhibitory effect of C. asiaticum on the growth of the HL-60/MX2 cells might arise from the induction of apoptosis. Treatment of HL-60/MX2 cells with the fractions markedly decreased the mRNA levels of the multi-drug resistance protein-1 and breast cancer resistance protein. The CHCI3 fraction and hexane fraction increased MX accumulation in HL-60/MX2 cells. These results imply that the CHCI3 fraction of C asiaticum plays a pivotal role as a chemosensitizer. We suggest that components of C asiaticum might have a therapeutic potential for the treatment of MDR leukemia.

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