Abstract
A resistant non-small cell lung carcinoma cell line-NSCLC (NCI-H460/R) was established in order to investigate the potential of sulfinosine (SF) to overcome multidrug resistance (MDR). The cytotoxicity of doxorubicin (DOX) in NCI-H460/R cells was enhanced by interaction with SF. SF improved the sensitivity of resistant cells to DOX when NCI-H460/R cells were pretreated with SF. Synergism was accompanied by the accumulation of cells in S and G(2)/M phases. Pretreatment with SF was more potent in improving the sensitivity to DOX than verapamil (VER). The decrease of mdr1 and topo II alpha expression (assessed by RT-PCR), was consistent with the DOX accumulation assay and cell cycle analysis. Also, SF significantly decreased intracellular glutathione (GSH) concentration. These results point to SF as a potential agent of MDR reversal and a valuable drug for improving chemotherapy of NSCLC.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / metabolism
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Antineoplastic Combined Chemotherapy Protocols / therapeutic use
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Binding, Competitive
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Carcinoma, Non-Small-Cell Lung / drug therapy*
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Cell Cycle / drug effects
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Cell Line, Tumor
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Cysteine / metabolism
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DNA Topoisomerases, Type II / metabolism
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Doxorubicin / administration & dosage
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Doxorubicin / pharmacokinetics
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Doxorubicin / pharmacology*
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Drug Resistance, Multiple / drug effects*
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Drug Resistance, Neoplasm / drug effects
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Drug Synergism
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Glutathione / metabolism
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Humans
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Lung Neoplasms / drug therapy*
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Multidrug Resistance-Associated Proteins / metabolism
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Purine Nucleosides / administration & dosage
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Purine Nucleosides / chemistry
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Purine Nucleosides / pharmacology*
Substances
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ABCB1 protein, human
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ATP Binding Cassette Transporter, Subfamily B
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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Multidrug Resistance-Associated Proteins
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Purine Nucleosides
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sulfinosine
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Doxorubicin
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DNA Topoisomerases, Type II
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Glutathione
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Cysteine
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multidrug resistance-associated protein 1