Abstract
Statins, anti-hypercholesterolemic agents, have previously been reported to induce apoptosis and exert antitumor activity when combined with other antitumor agents. The potential of lovastatin in combination with highly specific COX-2 inhibitor (MF-tricyclic) to induce anti-proliferative activity against tumour cells was evaluated using the combination index (CI) method. Murine colorectal cancer (colon-26, CMT-93), melanoma (B16F10) and human bladder carcinoma cells (T24) were tested. Exposure of colon-26 and CMT-93 cells resulted in synergistic interactions in both cell lines with CI<1 for 20-80% inhibition of cell growth in both cell lines. This synergy was not observed in the B16F10 melanoma and T24 bladder carcinoma cells. MF-tricyclic (40 microg/ml), augmented lovastatin-induced apoptosis up to 2.5-fold in colon-26 cancer cells. Combination of a specific COX-2 inhibitor, MF-tricyclic, may increase antiproliferative effects of lovastatin in colon cancer cells and this effect was due to an augmented apoptosis.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / drug therapy*
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Adenocarcinoma / metabolism
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Animals
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Antineoplastic Agents / pharmacology
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Apoptosis / drug effects
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Cell Division / drug effects
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Colorectal Neoplasms / drug therapy*
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Colorectal Neoplasms / metabolism
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Cyclooxygenase 2
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors / pharmacology*
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Drug Interactions
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Drug Synergism
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Drug Therapy, Combination
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Furans / pharmacology*
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Humans
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
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Isoenzymes / antagonists & inhibitors
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Lovastatin / pharmacology*
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Melanoma / drug therapy
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Melanoma / metabolism
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Membrane Proteins
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Mice
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Prostaglandin-Endoperoxide Synthases
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Tetrazolium Salts
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Thiazoles
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Tumor Cells, Cultured / drug effects*
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Tumor Cells, Cultured / metabolism
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Urinary Bladder Neoplasms / drug therapy
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Urinary Bladder Neoplasms / metabolism
Substances
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Antineoplastic Agents
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Cyclooxygenase 2 Inhibitors
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Cyclooxygenase Inhibitors
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Furans
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Isoenzymes
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Membrane Proteins
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Tetrazolium Salts
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Thiazoles
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3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2(5H)-furanone
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Lovastatin
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Cyclooxygenase 2
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PTGS2 protein, human
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Prostaglandin-Endoperoxide Synthases
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thiazolyl blue