The cytotoxicity of eutigosides from Eurya emarginata against HL-60 promyelocytic leukemia cells.
Two phenolic glucosides, eutigoside B and eutigoside C were isolated from the fresh leaves of Eurya 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 from E. emarginata on the growth of HL-60 appears to arise from the induction of apoptosis via the down-regulation of Bcl-2 and the activation of caspase.
Park
Soo Yeong
SY
Department of Medicine, Cheju National University, Jeju 690-756, Korea.
Yang
Hong Chul
HC
Moon
Ji Young
JY
Lee
Nam Ho
NH
Kim
Se Jae
SJ
Kang
Ji Hoon
JH
Lee
Young Ki
YK
Park
Deok Bae
DB
Yoo
Eun Sook
ES
Kang
Hee Kyoung
HK
D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000032:analysis; D003374:Coumarins; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018922:HL-60 Cells / Q000187:drug effects*; D006801:Humans; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D028242:Theaceae / Q000737:chemistry*
D000972:Antineoplastic Agents, Phytogenic; D003374:Coumarins; D005960:Glucosides; D010636:Phenols; D019253:Proto-Oncogene Proteins c-bcl-2; C505498:eutigoside A; C505499:eutigoside C; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases