Ways to enhance chemosensitizing of tumor cells with NO donors in tumor therapy with cytostatics and hydroxamic acids

Abstract

The influence of an organic NO donor belonging to non-steroidal anti-inflammatory drugs (NSAIDs) — NO-indomethacin (NO-Ind) on the antitumor effect of cyclophosphamide (CP) and its compositions with asparagyl hydroxamic acid (AHA) were studied, along with the influence on the activity of cytochrome P-450. Compared to a previously studied NSAID — diclofenac hydroxamic acid nitrate — NO-Ind exhibited lower enhancement of CP activity even when hydroxamic acid was added to the drug composition. EPR spectroscopy was used to evaluate the changes in activity of P-450 under the action of modified NSAIDs. The studies demonstrated partial inhibition of cytochrome P-450, the inhibition time is being greater for the first NSAID than for NO-Ind. The duration of P-450 inhibition under the action of different NO donors influences activity of CP.