The cytotoxicity of eutigosides fromEurya emarginata against HL-60 promyelocytic leukemia cells
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Two phenolic glucosides, eutigoside B and eutigoside C were isolated from the fresh leaves ofEurya emarginata. These two phenolic glucosides exerted a significant inhibitory effect on the growth of HL-60 promyelocytic leukemia cells. Furthermore, when the HL-60 cells were treated with eutigoside C, several apoptotic characteristics such as DNA fragmentation, morphologic changes, and increase of the population of sub-G1 hypodiploid cells were observed. In order to understand the mechanism of apoptosis induction by eutigoside C, we examined the changes of Bcl-2 and Bax expression levels. The eutigoside C reduced Bcl-2 protein and mRNA levels, but slightly increased Bax protein and mRNA levels in a time-dependent manner. When we examined the activation of caspase-3, an effector of apoptosis, the eutigoside C increased the expression of active form (19-kDa) of caspase-3 and the increase of their activities was demonstrated by the cleavage of poly (ADP-ribose) polymerase, a substrate of caspase-3, to 85-kDa. The results suggest that the inhibitory effect of eutigoside C fromE. emarginata on the growth of HL-60 appears to arise from the induction of apoptosisvia the down-regulation of Bcl-2 and the activation of caspase.
Key wordsEurya emarginata HL-60 Eutigosides B Eutigoside C Apoptosis. Bcl-2 Bax Caspase-3
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