Synergistic interaction between highly specific cyclooxygenase-2 inhibitor, MF-tricyclic and lovastatin in murine colorectal cancer cell lines.

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.

• Authors: Wojciech Feleszko, Ahmad Jalili, Dominika Olszewska, Izabela Mlynarczuk, Tomasz Grzela, Adam Giermasz, Marek Jakóbisiak
• Journal: Oncology reports (Oncol Rep) 2002 Jul-Aug Vol. 9 Issue 4 Pg. 879-85 ISSN: 1021-335X [Print] Greece
• PMID: 12066226 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors
• Furans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Isoenzymes
• Membrane Proteins
• Tetrazolium Salts
• Thiazoles
• 3-(3,4-difluorophenyl)-4-(4-(methylsulfonyl)phenyl)-2(5H)-furanone
• Lovastatin
• Cyclooxygenase 2
• PTGS2 protein, human
• Prostaglandin-Endoperoxide Synthases
• thiazolyl blue

Topics

• Adenocarcinoma (drug therapy, metabolism)
• Animals
• Antineoplastic Agents (pharmacology)
• Apoptosis (drug effects)
• Cell Division (drug effects)
• Colorectal Neoplasms (drug therapy, metabolism)
• Cyclooxygenase 2
• Cyclooxygenase 2 Inhibitors
• Cyclooxygenase Inhibitors (pharmacology)
• Drug Interactions
• Drug Synergism
• Drug Therapy, Combination
• Furans (pharmacology)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• Isoenzymes (antagonists & inhibitors)
• Lovastatin (pharmacology)
• Melanoma (drug therapy, metabolism)
• Membrane Proteins
• Mice
• Prostaglandin-Endoperoxide Synthases
• Tetrazolium Salts
• Thiazoles
• Tumor Cells, Cultured (drug effects, metabolism)
• Urinary Bladder Neoplasms (drug therapy, metabolism)