S-Space College of Veterinary Medicine (수의과대학) Dept. of Veterinary Medicine (수의학과) Journal Papers (저널논문_수의학과)
Cellular inactivation of nitric oxide induces p53-dependent apoptosis in human melanoma cells
- Moon, Seo Hyun; Cho, Myung-Haing; Kim, Min Young
- Issue Date
- Tropical Journal of Pharmaceutical Research, Vol.15 No.8, pp.1595-1603
- Purpose: To examine the role of endogenous nitric oxide (NO center dot) and influence of p53 status during apoptosis induced by a selective iNOS inhibitor, N-[(3-aminomethyl) benzyl] acetamidine (1400W), and/or an NO center dot scavenger carboxy-PTIO (c-PTIO) in two isogenic human melanoma cell lines, wild-type p53 (A375) and p53 mutant (SK mel-28) cells. Methods: 3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide (MTT) and Annexin V/propidium iodide assay were used to test for antiproliferation and apoptosis, respectively. Griess and reverse transcription-polymerase chain reaction (RT-PCR) reactions were carried out to assay NO center dot production and the mRNA levels of inhibitors of apoptosis (IAP). Results: c-PTIO and 1400W, alone or in combination, inhibited cell growth and promoted apoptosis via sub-G1 cell cycle arrest mediated by decrease in NO center dot. Apoptosis was delayed and greatly reduced in magnitude in SK mel-28 cells, underscoring the importance of p53 modulation of the response. In both cell types, apoptosis induced by iNOS inhibition and/or NO center dot depletion was blocked by an exogenous NO center dot donor, sodium nitroprusside. It was also found that inhibitors of apoptosis family (survivin, XIAP and cIAP1) were significantly depressed, which appear to play an important role in the regulation of p53-mediated apoptotic response under these conditions. Conclusion: The data obtained provide insight into the mechanism of cell proliferation action of endogenous NO center dot, based on p53 status, and indicate manipulation of iNOS may offer exciting opportunities to improve the effectiveness of melanoma treatment.
- Files in This Item: There are no files associated with this item.