Document Detail

Endogenously produced ganglioside GM3 endows etoposide and doxorubicin resistance by up-regulating Bcl-2 expression in 3LL Lewis lung carcinoma cells.
MedLine Citation:
PMID:  16571667     Owner:  NLM     Status:  MEDLINE    
The ganglioside patterns have been shown to dramatically change during cell proliferation and differentiation and in certain cell-cycle phases, brain development, and cancer malignancy. To investigate the significance of the ganglioside GM3 in cancer malignancy, we established GM3-reconstituted cells by transfecting the cDNA of GM3 synthase into a GM3-deficient subclone of the 3LL Lewis lung carcinoma cell line (Uemura, S. (2003) Glycobiology, 13, 207-216). The GM3-reconstituted cells were resistant to apoptosis induced by etoposide and doxorubicin. There were no changes in the expression levels of topoisomerase IIalpha or P-glycoprotein, or in the uptake of doxorubicin between the GM3-reconstituted cells and the mock-transfected cells. To understand the mechanism of the etoposide-resistant phenotype acquired in the GM3-reconstituted cells, we investigated their apoptotic signaling. Although no difference was observed in the phosphorylation of p53 at serine-15-residue site by etoposide between the GM3-reconstituted cells and mock-transfected cells, the activation of both caspase-3 and caspase-9 was specifically inhibited in the former. We found that the anti-apoptotic protein B-cell leukemia/lymphoma 2 (Bcl-2) was increased in the GM3-reconstituted cells. Moreover, wild-type 3LL Lewis lung carcinoma cells, which have an abundance of GM3, exhibited no DNA fragmentation following etoposide treatment and expressed higher levels of the Bcl-2 protein compared with the J5 subclone. Thus, these results support the conclusion that endogenously produced GM3 is involved in malignant phenotypes, including anticancer drug resistance through up-regulating the Bcl-2 protein in this lung cancer cell line.
Mariko Noguchi; Kazuya Kabayama; Satoshi Uemura; Byoung-won Kang; Masaki Saito; Yasuyuki Igarashi; Jin-ichi Inokuchi
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2006-03-29
Journal Detail:
Title:  Glycobiology     Volume:  16     ISSN:  0959-6658     ISO Abbreviation:  Glycobiology     Publication Date:  2006 Jul 
Date Detail:
Created Date:  2006-06-16     Completed Date:  2006-08-22     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  9104124     Medline TA:  Glycobiology     Country:  England    
Other Details:
Languages:  eng     Pagination:  641-50     Citation Subset:  IM    
Department of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
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MeSH Terms
Antineoplastic Agents / pharmacology*
Carcinoma, Lewis Lung / metabolism*
Caspase 3
Caspase 9
Caspases / antagonists & inhibitors
Ceramides / metabolism
Doxorubicin / pharmacology*
Drug Resistance, Neoplasm
Etoposide / pharmacology*
G(M3) Ganglioside / metabolism*
P-Glycoprotein / metabolism
Proto-Oncogene Proteins c-bcl-2 / metabolism*
Receptors, Tumor Necrosis Factor / physiology
Reg. No./Substance:
0/Antineoplastic Agents; 0/Ceramides; 0/G(M3) Ganglioside; 0/P-Glycoprotein; 0/Proto-Oncogene Proteins c-bcl-2; 0/Receptors, Tumor Necrosis Factor; 23214-92-8/Doxorubicin; 33419-42-0/Etoposide; EC 3.4.22.-/Casp3 protein, mouse; EC 3.4.22.-/Casp9 protein, mouse; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspase 9; EC 3.4.22.-/Caspases

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