A molecular basis for multidrug-resistance and reversal of resistance with human malignant cells

S. Akiyama, H. Kikuchi, Akihiko Yoshimura, M. Matsumoto

Research output: Contribution to journalArticle

Abstract

Development of cellular resistance to multiple types of anticancer agents has been recognized as one of the major obstacles for the effective cancer chemotherapy. Increased expression of mdr 1 mRNA seems to be a common mechanism for multidrug resistance (MDR) in human malignant cells. The product of the mdr 1 gene is P-glycoprotein. The predicted membrane orientation of the protein and homology with bacterial active transport proteins, and capability of the protein to bind hydrophobic anticancer agents are consistent with the function of P-glycoprotein as an energy-dependent efflux pump responsible for MDR phenotype. Most of the hydrophobic agents which overcome MDR are cationic and amphipathic. These agents interact with certain polar lipids and inhibit also the binding of hydrophobic anticancer agents with P-glycoprotein. They might directly bind to the binding site of anticancer agents on P-glycoprotein and competitively inhibit the binding of anticancer agents. Alternatively, they might bind to polar lipids of membrane vesicles and indirectly inhibit the binding ability of the protein to anticancer agents by perturbing the membrane function.

Original languageEnglish
Pages (from-to)2617-2625
Number of pages9
JournalJapanese Journal of Cancer and Chemotherapy
Volume14
Issue number9
Publication statusPublished - 1987 Sep
Externally publishedYes

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Multiple Drug Resistance
Antineoplastic Agents
P-Glycoprotein
Carrier Proteins
Active Biological Transport
Membrane Lipids
Membrane Proteins
Binding Sites
Phenotype
Lipids
Drug Therapy
Messenger RNA
Membranes
Genes
Neoplasms
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology

Cite this

A molecular basis for multidrug-resistance and reversal of resistance with human malignant cells. / Akiyama, S.; Kikuchi, H.; Yoshimura, Akihiko; Matsumoto, M.

In: Japanese Journal of Cancer and Chemotherapy, Vol. 14, No. 9, 09.1987, p. 2617-2625.

Research output: Contribution to journalArticle

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