Evaluation of the effects of nicorandil and its molecular precursor (without radical NO) on proliferation and apoptosis of 786-cell
Nicorandil is a nitric oxide (NO) donor used in the treatment of angina symptoms. It has also been reported to protect cells and affect the proliferation and death of cells in some tissues. The molecules that interfere with these processes can cause dysfunction in healthy tissues but can also assist in the therapy of some disorders. In this study we examined the effect of nicorandil and of the molecular precursor that does not have the NO radical (N-(beta-hydroxyethyl) nicotinamide) on the cell proliferation and death of human renal carcinoma cells (786-O) under normal oxygenation conditions. The molecular precursor was used in order to analyze the effects independents of NO. In the cytotoxicity test, nicorandil was shown to be cytotoxic at very high concentrations and it was more cytotoxic than its precursor (cytotoxic at concentrations of 2,000 and 3,000 μg/mL, respectively). We propose that the lower cytotoxicity of the precursor is due to the absence of the NO radical. In this study, the cells exposed to nicorandil showed neither statistically significant changes in cell proliferation nor increases in apoptosis or genotoxicity. The precursor generated similar results to those of nicorandil. We conclude that nicorandil causes no changes in the proliferation or apoptosis of the cell 786-O in normal oxygenation conditions. Moreover, the lack of NO radical in the precursor molecule did not show a different result, except in the cell cytotoxicity.
KeywordsNicorandil N-(beta-hydroxyethyl) nicotinamide 786-O cells Cell proliferation Apoptosis Cytotoxicity
We would like to thank the Coordination of Improvement of Higher Education Personnel (CAPES), National Council for Scientific and Technological Development (CNPq) and Araucaria Foundation for their financial support.
- Hiremath JG, Valluru R, Jaiprakash N, Katta SA, Matad PP (2010) Pharmaceutical aspects of Nicorandil. Int J Pharm Pharm Sci 2:24–29Google Scholar
- Huang Y-H, Shang B-Y, Zhen Y-S (2005) Antitumor efficacy of lidamycin on hepatoma and active moiety of its molecule. World J Gastroenterol 11:3980–3984Google Scholar
- Ishii H, Toriyama T, Aoyama T, Takahashi H, Yamada S, Kasuga H, Ichimiya S, Kanashiro M, Mitsuhashi H, Maruyama S, Matsuo S, Naruse K, Matsubara T, Murohara T (2007) Efficacy of oral nicorandil in patients with end-stage renal disease: a retrospective chart review after coronary angioplasty in Japanese patients receiving hemodialysis. Clin Ther 29–1:110–122CrossRefGoogle Scholar
- Kobayashi H (1995) A comparison between manual microscopic analysis and computerized image analysis in the single cell gel electrophoresis assay. MMS Commun 3:103–115Google Scholar
- Moncada S, Palmer RMJ, Higgs EA (1991) Nitric oxide: physiology, pathophysiology, and pharmacology. Pharmacol Rev 43:109–142Google Scholar
- Nagata K, Obata K, Odashima M, Yamada A, Somura F, Nishizawa T, Ichihara S, Izawa H, Iwase M, Hayakawa A, Murohara T, Yokota M (2003) Nicorandil inhibits oxidative stress-induced apoptosis in cardiac myocytes through activation of mitochondrial ATP-sensitive potassium channels and a nitrate-like effect. J Mol Cell Cardiol 35:1505–1512CrossRefGoogle Scholar
- Panis C, Mazzuco TL, Costa CZF, Victorino VJ, Tatakihara VLH, Yamauchi LM, Yamada-Ogatta SF, Cecchini R, Rizzo LV, Pinge-Filho P (2010) Trypanosoma cruzi: effect of the absence of 5-lipoxygenase (5-LO)-derived leukotrienes on levels of cytokines, nitric oxide and iNOS expression in cardiac tissue in the acute phase of infection in mice. Exp Parasitol 127:58–65CrossRefGoogle Scholar
- Rovozzo GC, Burke CN (1973) A manual of basic virological techniques. Prentice-Hall, Englewood CliffsGoogle Scholar
- Sudo H, Hirata M, Kanada H, Yorozu K, Tashiro Y, Serizawa K-I, Yogo K, Kataoka M, Moriguchi Y, Ishizuka N (2009) Nicorandil improves glomerular injury in rats with mesangioproliferative glomerulonephritis via inhibition of proproliferative and profibrotic growth factors. J Pharmacol Sci 111:53–59CrossRefGoogle Scholar
- Yim CY et al (1993) Macrophage nitric oxide synthesis delays progression of ultraviolet light induced murine Skin Cancers. Cancer Res 53:5507–5511Google Scholar
- Zhang T, Otevrel T, Gao Z, Gao Z, Ehrlich SM, Fields JZ, Boman BM (2001) Evidence that APC regulates survivin expression: a possible mechanism contributing to the stem cell origin of colon cancer. Cancer Res 61:8664–8667Google Scholar