Medroxyprogesterone-acetate reverses the MDR phenotype of the CG5-doxorubicin resistant human breast cancer cell line

C. Zibera, N. Gibelli, L. Maestri, G. Robustelli della Cuna

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

In malignant cells multidrug resistance (MDR) is frequently associated with the expression of a 170 KDa P-glycoprotein (P-gp) in the plasma membrane. P-gp acts as an ATP-dependent efflux pump causing a decreased intracellular accumulation of structurally unrelated natural anticancer agents such as anthracyclines. Doxorubicin (DX) resistance is mostly related to the multidrug resistance gene product P-gp. In our experiments the revertant activity of medroxyprogesterone acetate (MPA) in comparison to that of the well known revertant agent verapamil (VRP) was investigated. In vitro tests were carried out on a DX-resistant variant (CG5/DX) obtained in our laboratory from the parenteral CG5 human breast cancer cell line by continuous exposure to the drug. The ability of MPA to modulate intracellular DX accumulation and to reverse MDR was evaluated. MPA appeared more active than VRP in reversing MDR, suggesting a possible role of this synthetic progestin as chemosensitizing agent in the clinical menagement of anthracycline-resistant breast cancer.

Original languageEnglish
Pages (from-to)745-749
Number of pages5
JournalAnticancer Research
Volume15
Issue number3
Publication statusPublished - 1995

Fingerprint

Medroxyprogesterone Acetate
Multiple Drug Resistance
Doxorubicin
P-Glycoprotein
Breast Neoplasms
Phenotype
Cell Line
Anthracyclines
Verapamil
Progesterone Congeners
MDR Genes
Antineoplastic Agents
Adenosine Triphosphate
Cell Membrane
Pharmaceutical Preparations

Keywords

  • Breast cancer
  • Medroxyprogesterone-acetate
  • Multidrug resistance
  • P-glycoprotein

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Medroxyprogesterone-acetate reverses the MDR phenotype of the CG5-doxorubicin resistant human breast cancer cell line. / Zibera, C.; Gibelli, N.; Maestri, L.; Robustelli della Cuna, G.

In: Anticancer Research, Vol. 15, No. 3, 1995, p. 745-749.

Research output: Contribution to journalArticle

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AU - Robustelli della Cuna, G.

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AB - In malignant cells multidrug resistance (MDR) is frequently associated with the expression of a 170 KDa P-glycoprotein (P-gp) in the plasma membrane. P-gp acts as an ATP-dependent efflux pump causing a decreased intracellular accumulation of structurally unrelated natural anticancer agents such as anthracyclines. Doxorubicin (DX) resistance is mostly related to the multidrug resistance gene product P-gp. In our experiments the revertant activity of medroxyprogesterone acetate (MPA) in comparison to that of the well known revertant agent verapamil (VRP) was investigated. In vitro tests were carried out on a DX-resistant variant (CG5/DX) obtained in our laboratory from the parenteral CG5 human breast cancer cell line by continuous exposure to the drug. The ability of MPA to modulate intracellular DX accumulation and to reverse MDR was evaluated. MPA appeared more active than VRP in reversing MDR, suggesting a possible role of this synthetic progestin as chemosensitizing agent in the clinical menagement of anthracycline-resistant breast cancer.

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