Sulfinosine enhances doxorubicin efficacy through synergism and by reversing multidrug resistance in the human non-small cell lung carcinoma cell line (NCI-H460/R).

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.

• Authors: Milica Pesić, Tijana Andjelković, Jasna Banković, Ivanka D Marković, Ljubisa Rakić, Sabera Ruzdijić
• Journal: Investigational new drugs (Invest New Drugs) Vol. 27 Issue 2 Pg. 99-110 (Apr 2009) ISSN: 1573-0646 [Electronic] United States
• PMID: 18493718 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ABCB1 protein, human
• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1
• Multidrug Resistance-Associated Proteins
• Purine Nucleosides
• sulfinosine
• Doxorubicin
• DNA Topoisomerases, Type II
• Glutathione
• Cysteine
• multidrug resistance-associated protein 1

Topics

• ATP Binding Cassette Transporter, Subfamily B
• ATP Binding Cassette Transporter, Subfamily B, Member 1 (metabolism)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Binding, Competitive
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Cell Cycle (drug effects)
• Cell Line, Tumor
• Cysteine (metabolism)
• DNA Topoisomerases, Type II (metabolism)
• Doxorubicin (administration & dosage, pharmacokinetics, pharmacology)
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Drug Synergism
• Glutathione (metabolism)
• Humans
• Lung Neoplasms (drug therapy)
• Multidrug Resistance-Associated Proteins (metabolism)
• Purine Nucleosides (administration & dosage, chemistry, pharmacology)