Inhibition of ERK and Activation of p38 are Involved in Diallyl Disulfide Induced Apoptosis of Leukemia HL-60 Cells

다국어 초록 (Multilingual 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.

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