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 cytotoxic effector. In the present work, two chemically different NO-donors such as glyceryl trinitrate (GTN) and S-nitroso-N-acetylpenicillamine (SNAP) were evaluated for both NO release and cytostatic/cytotoxic properties. 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 greater release of NO derived from GTN in presence of cells compared to the values observed in the media, confirming that the release of NO by GTN can be enzymatic and non-enzymatic. On the contrary, SNAP generated NO without contribution of cellular components and saturated oxyhemoglobin quickly, within 2 hours. Both NO-donors inhibited thymidine incorporation 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 microM induced only a 33% cytostatic effect. About trypan blue exclusion test, after 24 h GTN and SNAP, releasing similar amounts of NO, showed comparable cytotoxic effects on U251 cells (50% dead cells), but not on MCF-7 cells, where GTN resulted more cytotoxic. From our data, the "in 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.
Adami
A
A
Institute of Pharmacology, University of Verona, Italy.
Crivellente
F
F
De Prati
A C
AC
Cavalieri
E
E
Cuzzolin
L
L
Tommasi
M
M
Suzuki
H
H
Benoni
G
G
D001711:Biotransformation; D001932:Brain Neoplasms / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000633:toxicity*; D005260:Female; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D007700:Kinetics; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000493:pharmacokinetics / Q000633:toxicity*; D005996:Nitroglycerin / Q000493:pharmacokinetics / Q000633:toxicity*; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000633:toxicity; D026423:S-Nitroso-N-Acetylpenicillamine; D014407:Tumor Cells, Cultured
D004791:Enzyme Inhibitors; D020030:Nitric Oxide Donors; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D005996:Nitroglycerin; D010396:Penicillamine