Synergistic interaction between highly specific cyclooxygenase-2 inhibitor, MF-tricyclic and lovastatin in murine colorectal cancer cell lines.
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.
Feleszko
Wojciech
W
Department of Immunology, Centre of Biostructure Research, The Medical University of Warsaw, Poland. wfeleszk@ib.amwaw.edu.pl
Jalili
Ahmad
A
Olszewska
Dominika
D
Mlynarczuk
Izabela
I
Grzela
Tomasz
T
Giermasz
Adam
A
Jakóbisiak
Marek
M
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology*; D004347:Drug Interactions; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005663:Furans / Q000494:pharmacology*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008148:Lovastatin / Q000494:pharmacology*; D008545:Melanoma / Q000188:drug therapy / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases; D013778:Tetrazolium Salts; D013844:Thiazoles; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000378:metabolism
D000970:Antineoplastic Agents; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005663:Furans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007527:Isoenzymes; D008565:Membrane Proteins; D013778:Tetrazolium Salts; D013844:Thiazoles; C102563:3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2(5H)-furanone; D008148:Lovastatin; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C022616:thiazolyl blue