[Diallyl disulfide-induced G2/M arrest of human gastric cancer MGC803 cells involves activation of p38 MAP kinase pathways].

Background & Objective: p38 MAP kinase signal transduction pathway was thought to be involved in the G(2)/M arrest,however,the involved mechanisms were not clear. This study was designed to determine the role of p38 MAP kinase signal transduction pathways in diallyl disulfide (DADS)-induced G(2)/M arrest in human gastric cancer MGC803 cells and its related molecular mechanisms.

Methods: MGC803 cells 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 blot analysis.

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 for 24 hours increased in the percentage of cells arrested in the G(2)/M phase from 9.3% to 39.4%(P< 0.05). Whereas in the presence of SB203580 the percentage decreased nearly one time, from 39.4% to 21.2% (P< 0.05). Western blot analysis showed that phosphorylation of p38 was increased 3.52-folds following treatment of MGC803 cells with 30 mg/L DADS for 20 minutes. At the same time, the total p38 abundance did not change. DADS treatment of MGC803 cells for 24 hours decreased the level of Cdc25C by 68%, and pretreatment of MGC803 cells with SB203580 partially reversed the downregulation of Cdc25C level by DADS (P< 0.05).

Conclusion: DADS- induced G(2)/M arrest of MGC803 cells involves the activation of p38 MAP kinase pathway. Decreased Cdc25C protein expression by p38 played a crucial role in G(2)/M arrest after the treatment with DADS.