Inhibition of ERK and activation of p38 are involved in diallyl disulfide induced apoptosis of leukemia HL-60 cells

Hui Tan; Hui Ling; Jie He; Lan Yi; Jianguo Zhou; Min Lin; Qi Su

doi:10.1007/s12272-001-1227-0

Inhibition of ERK and activation of p38 are involved in diallyl disulfide induced apoptosis of leukemia HL-60 cells

Arch Pharm Res. 2008 Jun;31(6):786-93. doi: 10.1007/s12272-001-1227-0. Epub 2008 Jun 19.

Authors

Hui Tan¹, Hui Ling, Jie He, Lan Yi, Jianguo Zhou, Min Lin, Qi Su

Affiliation

¹ Cancer Research Institute, University of South China, Hengyang City, Hunan Province, 421001, P.R.China. tanhuiy@sohu.com

PMID: 18563362
DOI: 10.1007/s12272-001-1227-0

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Allyl Compounds / pharmacology*
Antineoplastic Agents, Phytogenic / pharmacology*
Apoptosis / drug effects*
Blotting, Western
Cell Proliferation / drug effects
Cell Shape / drug effects
Cell Survival / drug effects
Disulfides / pharmacology*
Dose-Response Relationship, Drug
Enzyme Activation
Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors*
Extracellular Signal-Regulated MAP Kinases / metabolism
Flavonoids / pharmacology
Flow Cytometry
HL-60 Cells
Humans
Imidazoles / pharmacology
Leukemia, Promyelocytic, Acute / enzymology
Leukemia, Promyelocytic, Acute / pathology*
Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
Mitogen-Activated Protein Kinase 3 / metabolism
Phosphorylation
Protein Kinase Inhibitors / pharmacology*
Pyridines / pharmacology
Signal Transduction / drug effects*
Time Factors
p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
p38 Mitogen-Activated Protein Kinases / metabolism*

Substances

Allyl Compounds
Antineoplastic Agents, Phytogenic
Disulfides
Flavonoids
Imidazoles
Protein Kinase Inhibitors
Pyridines
diallyl disulfide
Extracellular Signal-Regulated MAP Kinases
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase 3
p38 Mitogen-Activated Protein Kinases
SB 203580
2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one