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

Toxicol Res. 2008 Mar;24(1):29-36. doi: 10.5487/TR.2008.24.1.029. Epub 2008 Mar 1.

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.

Keywords: Apoptosis; BCRR; Chemosensitizer; Crinum asiaticum; HL-60/MX2; MRP-1.