Effect of non-steroidal anti-inflammatory drugs on colon carcinoma Caco-2 cell responsiveness to topoisomerase inhibitor drugs.
Numerous studies demonstrate that the chemopreventive effect of non-steroidal anti-inflammatory drugs on colon cancer is mediated through inhibition of cell growth and induction of apoptosis. For these effects non-steroidal anti-inflammatory drugs have been recently employed as sensitising agents in chemotherapy. We have shown previously that treatments with aspirin and NS-398, a cyclo-oxygenase-2 selective inhibitor, affect proliferation, differentiation and apoptosis of the human colon adenocarcinoma Caco-2 cells. In the present study, we have evaluated the effects of aspirin and NS-398 non-steroidal anti-inflammatory drugs on sensitivity of Caco-2 cells to irinotecan (CPT 11) and etoposide (Vp-16) topoisomerase poisons. We find that aspirin co-treatment is able to prevent anticancer drug-induced toxicity, whereas NS-398 co-treatment poorly affects anticancer drug-induced apoptosis. These effects correlate with the different ability of aspirin and NS-398 to interfere with cell cycle during anticancer drug co-treatment. Furthermore, aspirin treatment is associated with an increase in bcl-2 expression, which persists in the presence of the anticancer drugs. Our data indicate that aspirin, but not NS-398, determines a cell cycle arrest associated with death suppression. This provides a plausible mechanism for the inhibition of apoptosis and increase in survival observed in anticancer drug and aspirin co-treatment.
Ricchi
P
P
Dipartimento di Biologia e Patologia Cellulare e Molecolare L. Califano, Istituto di Endocrinologia ed Oncologia Sperimentale G. Salvatore del Consiglio Nazionale delle Ricerche, Università Federico II, Via S. Pansini 5, 80131 Naples, Italy.
Di Matola
T
T
Ruggiero
G
G
Zanzi
D
D
Apicella
A
A
di Palma
A
A
Pensabene
M
M
Pignata
S
S
Zarrilli
R
R
Acquaviva
A M
AM
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001241:Aspirin / Q000494:pharmacology*; D018938:Caco-2 Cells; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D002470:Cell Survival; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D000077146:Irinotecan; D009578:Nitrobenzenes / Q000494:pharmacology*; D013449:Sulfonamides / Q000494:pharmacology*; D059003:Topoisomerase Inhibitors
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; D059003:Topoisomerase Inhibitors; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D005047:Etoposide; D000077146:Irinotecan; D001241:Aspirin; D002166:Camptothecin