Document Detail

Elevated phosphorylation of Chk1 and decreased phosphorylation of Chk2 are associated with abrogation of G2/M checkpoint control during transformation of Syrian hamster embryo (SHE) cells by Malachite green.
MedLine Citation:
PMID:  16085357     Owner:  NLM     Status:  MEDLINE    
Malachite green (MG), consisting of green crystals with a metallic lustre, is highly soluble in water, cytotoxic to various mammalian cells and also acts as a liver tumor promoter. In view of its industrial importance and possible exposure to human beings, MG poses a potential environmental health hazard. We have earlier reported the malignant transformation of Syrian hamster embryo (SHE) cells in primary culture by MG. In this study, we have studied the ability of MG to cause DNA damage, cell cycle arrest in mimosine synchronised and the possible roles of Chk1, Chk2, Cdc2, Cdc25C, 14-3-3 and Cyclin B1 in control and MG transformed SHE cells in order to understand the differential mechanisms associated with G2/M checkpoint control. Exposure of MG to control and transformed cells causes DNA damage. Flow cytometric analysis of mimosine synchronised cells when exposed to MG showed an increase of G2/M phase in control cells whereas no such accumulation of cells at the G2/M phase was observed in response to MG in transformed cells. Western blots of phosphoactive forms of Chk1 and Chk2 cells showed opposing levels. Control cells treated with MG showed a decrease in Chk1 and increase in Chk2, whereas the transformed cells treated with MG showed an increase in Chk1 and decrease in Chk2. Also a decrease in Cdc25C, 14-3-3 and Cyclin B1 was observed in MG treated transformed cells, whereas MG treated control cells showed elevated levels. Stabilization of the proteins seems to be the possible mechanism. The present study indicates elevated phosphorylation of Chk1 and decreased phosphorylation of Chk2 and decreased levels of Cyclin B1 are the critical changes associated with abrogation of G2/M checkpoint control during transformation of SHE cells by MG.
Hima Ashra; K V K Rao
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2005-08-08
Journal Detail:
Title:  Cancer letters     Volume:  237     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-06-01     Completed Date:  2006-07-31     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  188-98     Citation Subset:  IM    
Chemical Carcinogenesis Group, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410208, India.
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MeSH Terms
14-3-3 Proteins / biosynthesis
Cell Cycle
Cell Cycle Proteins / biosynthesis
Cell Transformation, Neoplastic
Coloring Agents / pharmacology
Cyclin B / biosynthesis
Cyclin B1
DNA Damage
Protein Kinases / chemistry*,  metabolism*
Protein-Serine-Threonine Kinases / chemistry*,  metabolism*
Rosaniline Dyes / pharmacology
cdc25 Phosphatases / biosynthesis
Reg. No./Substance:
0/14-3-3 Proteins; 0/CCNB1 protein, human; 0/Cell Cycle Proteins; 0/Coloring Agents; 0/Cyclin B; 0/Cyclin B1; 0/Rosaniline Dyes; 10309-95-2/malachite green; EC 2.7.-/Protein Kinases; EC kinase 2; EC kinase 1; EC Kinases; EC protein, human; EC Phosphatases

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