Cobalamin potentiates vinblastine cytotoxicity through downregulation of mdr-1 gene expression in HepG2 cells.

Cobalamin potentiates vinblastine cytotoxicity through downregulation of mdr-1 gene expression in HepG2 cells. Research Abstract Details 

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Cobalamin potentiates vinblastine cytotoxicity through downregulation of mdr-1 gene expression in HepG2 cells. Abstract Text:

V Eacute Ronique Marguerite,Myl Eacute Ne Beri-Dexheimer,Sandrine Ortiou,Jean-Louis Gu Eacute Ant,Marc Merten,V Eacute Ronique Marguerite,Myl Eacute Ne Beri-Dexheimer,Sandrine Ortiou,Jean-Louis Gu Eacute Ant,Marc Merten, Marguerite, Beri-Dexheimer,Sandrine Ortiou,Jean-Louis ,Marc Merten,

BACKGROUND: P-glycoprotein (Pgp), produced by multidrug resistance-1 gene (mdr-1), is a main mechanism developed by cancer cells to guard against anti-cancer drugs. Alterations of DNA methylation of the mdr-1 gene promoter are known to be linked to mdr-1 gene expression and are probably related to intracellular S-adenosyl-methionine. We here used HepG2 cells to determine the role of the methionine cycle (through the use of the Methionine-Synthase (MS) cofactor, cobalamin) on mdr-1 gene expression. METHODS: Semiquantitative RT-PCR of mdr-1 gene, cellular retention of rhodamine-123, and vinblastine cytotoxicity were carried out on cells cultivated with and without cobalamin. Methylation status of the mdr-1 gene promoter was determined by methylation-specific PCR. RESULTS: Addition of cobalamin to the cells led to an increase in MS activity, to a significant decrease in mdr-1 gene expression which is correlated to an increase in retention of the Pgp substrate Rhodamine 123. Furthermore, cobalamin potentiated cell sensitivity to vinblastine to the same range as that of the Pgp blocker verapamil and prevented methotrexate-induced up-regulation of mdr-1 gene expression. However, no modification in methylation of the mdr-1 gene promoter was observed. CONCLUSION: Cobalamin downregulates mdr-1 gene expression, as well as Pgp expression and function, and significantly increases cytotoxicity of vinblastine. The identification of this novel way of diminishing cellular resistance to the chemotherapeutic agent vinblastine holds promises of leading to better treatments for cancer patients.

Cobalamin potentiates vinblastine cytotoxicity through downregulation of mdr-1 gene expression in HepG2 cells. Publishing Authors By Initials

VE Marguerite,ME Beri-Dexheimer,S Ortiou,JL Gu Eacute Ant,M Merten,VE Marguerite,ME Beri-Dexheimer,S Ortiou,JL Gu Eacute Ant,M Merten,V Marguerite,M Beri-Dexheimer,S Ortiou,JL ,M Merten,

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Cobalamin potentiates vinblastine cytotoxicity through downregulation of mdr-1 gene expression in HepG2 cells. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cellular physiology and biochemistry : internation

VOLUME: 20

Page Numbers: 967-76

Journal Abbreviation: Cell. Physiol. Biochem.

ISSN: 1015-8987

DAY: 5

MONTH: 11

YEAR: 2007

Cobalamin potentiates vinblastine cytotoxicity through downregulation of mdr-1 gene expression in HepG2 cells. Information

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LANGUAGE: eng

NlmUniqueID: 9113221

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AFFILIATION: Laboratoire de Pathologie Cellulaire et Moleculaire en Nutrition, Faculté de Médecine, University Henry Poincaré, Vandoeuvre-les-Nancy, Cedex, France.

Country: Switzerland

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MEDLINETA: Cell Physiol Biochem

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