BIOTRANSFORMATION AND CYTOTOXIC PROPERTIES OF NO-DONORS ON MCF7 AND U251 CELL-LINES

Previous studies have shown a role for nitric oxide (NO) as a cytotoxi c effector. In the present work, two chemically different NO-donors su ch as glyceryl trinitrate (GTN) and S-nitroso-N-acetylpenicillamine (S NAP) were evaluated for both NO release and cytostatic/cytotoxic prope rties. Nitrite accumulation in the supernatant of MCF-7 and U251 cell lines indicated a greater and quickly release of NO derived from SNAP. A time-course of hemoglobin absorption spectral changes showed a grea ter release of NO derived from GTN in presence of cells compared to th e values observed in the media, confirming that the release of NO by G TN can be enzymatic and non-enzymatic. On the contrary, SNAP generated NO without contribution of cellular components and saturated oxyhemog lobin quickly, within 2 hours. Both NO-donors inhibited thymidine inco rporation in a similar manner and dose-dependently in U251 cells, but not in MCF-7 cells, where SNAP at the highest tested dose of 1000 mu M induced only a 33% cytostatic effect. About trypan blue exclusion tes t, after 24 h GTN and SNAP, releasing similar amounts of NO, showed co mparable cytotoxic effects on U251 cells (50% dead cells), but not on MCF-7 cells, where GTN resulted more cytotoxic. From our data, the ''i n vitro'' antitumoral activity of NO-donors seems to be related to the type of tumor cell lines, to the amount and duration of NO release.