|
KMID : 0043320080310060756
|
|
Archives of Pharmacal Research
2008 Volume.31 No. 6 p.756 ~ p.793
|
|
|
Inhibition of ERK and Activation of p38 are Involved in Diallyl Disulfide Induced Apoptosis of Leukemia HL-60 Cells
|
|
Tan Hui
Ling Hui
He Jie
Yi Lan
Zhou Jianguo
Lin Min
Su Qi
|
|
|
Abstract
|
|
|
|
We investigated the effects of diallyl disulfide (DADS) on the induction of apoptosis in human Leukemia cell line HL-60 and explored the roles of mitogen-activated protein kinase (ERK and p38 MAPK) pathways in the growth inhibition and apoptosis induced by DADS. MTT assay was used to determine the DADS induced cell growth inhibition in HL-60 cells. Flow cytometry and DNA fragmentation were used to examine the roles of apoptosis in DADS-mediated cell death. Western blot analysis of the expression of phospho-MAPKs (ERK and p38) was employed to elucidate the possible mechanisms of DADS induced apoptosis. We found that growth inhibition of HL-60 cells treated with DADS exhibited a dose-dependent response (P<0.05) and DADS induced significant apoptosis. DADS at the concentration of 10 mg/L persistently activated p38 and simultaneously reduced ERK activity. PD98059, an inhibitor of ERK upstream activators MAPK kinase MKK1 and MKK2, promoted cytotoxicity and apoptosis in HL-60 cells treated with DADS. In contrast, SB203580, an inhibitor of p38, decreased cytotoxicity and apoptosis induced by DADS. Therefore, DADS can effectively inhibit the proliferation and induce apoptosis of human leukemia cell line HL-60. Inhibition of ERK signaling pathways and activation of p38 signaling pathways are likely involved in DADS induced apoptosis in HL-60 cells.
|
|
|
KEYWORD
|
|
|
Diallyl disulfide, Leukemia, Apoptosis, MAPK
|
|
|
FullTexts / Linksout information
|
|
|
|
|
|
Listed journal information
|
|
  
|