Effect of dimethylsulfoxide on the proliferation and glycosaminoglycan synthesis of rat prostate adenocarcinoma cells (PAIII) in vitro: isolation and characterization of DMSO-resistant cells.
Dimethylsulfoxide (DMSO) modulates the tumorigenicity and other characteristics of some malignant cell lines in vitro. We have investigated DMSO effects on cell proliferation and glycosaminoglycan (GAG) synthesis in rat prostate adenocarcinoma (PAIII) cells in culture. DMSO inhibited cell proliferation and GAG synthesis and shedding. Cells that survived the initial exposure to 2.5% DMSO could be propagated in this concentration of the agent and were designated PAIII-DMSO resistant (PAIII-DMSOr). PAIII-DMSOr cells showed reversible indications of increased differentiation such as decreased growth rate and saturation density. Although the PAIII-DMSOr cells were grown in 2.5% DMSO, they had normal or elevated GAG content. The major GAG of both PAIII and PAIII-DMSOr cells was undersulfated heparan sulfate. Verapamil, a calcium channel blocker that reverses drug resistance in tumor cells, stimulated the growth of PAIII-DMSOr cells in the presence of 2.5% DMSO, but was inhibitory in the absence of DMSO. Growth of PAIII cells was inhibited by the differentiating agents sodium butyrate and retinoic acid and by the ionophore monensin. Interestingly, growth of PAIII-DMSOr cells in the presence of 2.5% DMSO was largely unaffected by sodium butyrate or retinoic acid. The results suggest that (1) PAIII-DMSOr cells arise from the induction of a compensation mechanism to DMSO effects in a preexisting population of cells: (2) there is a correlation between GAG synthesis and cell proliferation; and (3) further study of the verapamil effect may help elucidate the mechanism of the DMSO-induced differentiation of cancer cells.
Kaneski
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Developmental and Metabolic Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892.
Constantopoulos
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Brady
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D000230:Adenocarcinoma / Q000378:metabolism*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects*; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D004351:Drug Resistance; D004588:Electrophoresis, Cellulose Acetate; D006025:Glycosaminoglycans / Q000096:biosynthesis* / Q000302:isolation & purification; D066298:In Vitro Techniques; D008297:Male; D008985:Monensin / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured; D014700:Verapamil / Q000494:pharmacology
D000970:Antineoplastic Agents; D006025:Glycosaminoglycans; D008985:Monensin; D014700:Verapamil; D004121:Dimethyl Sulfoxide