Diallyl disulfide-induced G2/M arrest of human gastric cancer MGC803 cells involves activation of p38 MAP kinase pathways.
OBJECTIVE
To determine the role of p38 MAP kinase signal transduction pathways in diallyl disulfide (DADS)-induced G2/M arrest in human gastric cancer MGC803 cells.


METHODS
MGC803 cell growth inhibition was measured by MTT assay. Phase distribution of cell cycle was analyzed by flow cytometry. Expression of Cdc25C, p38, phosphorylation of p38 (pp38) were determined by Western blotting.


RESULTS
MTT assay showed that SB203580, a specific p38 MAPK inhibitor blocked DADS-induced growth inhibition. Flow cytometry analysis revealed that treatment of MGC803 cells with 30 mg/L DADS increased the percentage of cells in the G2/M phase from 9.3% to 39.4% (P<0.05), whereas inhibition of p38 activity by SB203580 abolished induction of G2/M arrest by DADS. Western blotting showed that phosphorylation of p38 was increased 3.52-fold following treatment of MGC803 cells with 30 mg/L DADS for 20 min (P<0.05), whereas Cdc25C was decreased 68% following treatment of MGC803 cells with 30 mg/L DADS for 24 h (P<0.05). Decreased Cdc25C protein expression by DADS was attenuated by SB203580 (P<0.05).


CONCLUSIONS
DADS-induced G2/M arrest of MGC803 cells involves activation of p38 MAP kinase pathways. Decreased Cdc25C protein expression by p38 MAPK played a crucial role in G2/M arrest after treatment with DADS.
Yuan
Jing-Ping
JP
Department of Pathology, Central Hospital of Wuhan, Wuhan 430014, Hubei Province, China.
Wang
Gui-Hua
GH
Ling
Hui
H
Su
Qi
Q
Yang
Yue-Hong
YH
Song
Ying
Y
Tang
Rong-Jun
RJ
Liu
Yao
Y
Huang
Chen
C
D000498:Allyl Compounds / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004220:Disulfides / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D013274:Stomach Neoplasms; D020687:cdc25 Phosphatases / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000498:Allyl Compounds; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D004220:Disulfides; C028009:diallyl disulfide; D048051:p38 Mitogen-Activated Protein Kinases; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases