These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: P53 and p38 MAPK pathways are involved in MONCPT-induced cell cycle G2/M arrest in human non-small cell lung cancer A549.
    Author: Zhang C, Zhu H, Yang X, Lou J, Zhu D, Lu W, He Q, Yang B.
    Journal: J Cancer Res Clin Oncol; 2010 Mar; 136(3):437-45. PubMed ID: 19727814.
    Abstract:
    PURPOSE: In previous research, we found that 10-methoxy-9-nitrocamptothecin (MONCPT) possessed potent anti-tumor activity in A549 cells in vitro and in vivo. In this paper, our purpose is to investigate the mechanism of MONCPT-induced cell cycle arrest in A549 cells. METHODS: Cell cycle distribution was measured using flow cytometry (FCM). Protein expression and RNA expression were analyzed by western blotting and real-time PCR, respectively. SiRNA technology was introduced to silence the expression of p53 and p38. RESULTS: FCM showed that MONCPT induced cell cycle G2/M arrest in time- and dose-dependent manner. The levels of feedback loop proteins PLK-1, Cdc25C, and cyclinB1 were obviously increased from 12 to 24 h, and then reduced from 36 to 48 h by MONCPT (100.0 nM). Moreover, down-regulation of p-AKT in A549 cells was seen after treated with 100.0 nM MONCPT for 12-48 h. Over-expression of p53 and p21 in A549 cells treated with MONCPT was observed in time-dependent manner. When wild type p53 expression was specifically inhibited by RNA-interference, A549 cells treated with MONCPT delayed the onset of G2/M arrest; meanwhile p-ERK and Cdc2 were up-regulated while p21 and CDK7 were down-regulated in A549 cells treated with MONCPT and p53 SiRNA transfection in contrast to cells treated with 100.0 nM MONCPT alone. In addition, our results exhibited that MONCPT obviously down-regulated p-ERK, JNK, p-JNK, and p-p38. Treatment with p38 mitogen-activated protein kinase (MAPK) SiRNA obviously inhibited p38 MAPK and delayed the G2/M arrest induced by 50.0 nM MONCPT after 48 h. CONCLUSION: Cell cycle regulators, AKT, p53, and MAPK, as therapeutic targets for MONCPT to induce cell cycle G2/M arrest in the context of anticancer therapy.
    [Abstract] [Full Text] [Related] [New Search]