Sergio Grando
Dermatology, School of Medicine
Phone: (949) 824-2713
Email: sgrando@uci.edu
http://www.hs.uci.edu/dermatology/Grando-Bio+Res%20Intrst.pdf
http://www.hs.uci.edu/dermatology/Faculty.aspx?id=106
Sergio Grando
Mucocutaneous keratinocytes and bronchial epithelial cells express nicotinic acetylcholine receptors (nAChRs). Emerging evidence indicates that nAChRs can be stimulated also by the tobacco-derived nitrosamines 4-(methylnitrosamino)-1-(3pyridyl)-1-butanone (NNK) and N'-nitrosonornicotine (NNN) that can induce tumors in laboratory animals. Nitrosamines may disturb the delicate balance between cell proliferation, growth arrest and apoptosis. A novel paradigm of cell regulation via nAChR has been discovered in studies of SLURP (secreted mammalian Ly-6/urokinase plasminogen activator receptor-related protein)-1 and -2. Experimental results suggest that SLURP-1 and -2 regulate keratinocyte proliferation, apoptosis and differentiation. Most importantly, SLURPs and professional nicotinic antagonists can abolish, in part, the abilities of NNK and NNN to cause tumorigenic transformation of immortalized keratinocytes. Learning the pharmacology of the nitrosamine vs. SLURP action on epithelial cells may help develop an effective anti-cancer treatment and prevention programs wherein hazardous effects of tobacco products are anticipated, or even abolished by a pharmacologic ligand of specific nicotinic receptor acting as an antidote.
Selected Publications:
Arredondo, J., Chernyavsky, A. I., and Grando, S. A. (2006). The nicotinic receptor antagonists abolish pathobiologic effects of tobacco-derived nitrosamines on BEP2D cells. J Cancer Res Clin Oncol 132(10), 653-63.
Arredondo, J., Chernyavsky, A. I., and Grando, S. A. (2006). Nicotinic receptors mediate tumorigenic action of tobacco-derived nitrosamines on immortalized oral epithelial cells. Cancer Biol Ther 5(5), 511-7.
Arredondo, J., Chernyavsky, A. I., and Grando, S. A. (2007). Overexpression of SLURP-1 and -2 alleviates the tumorigenic action of tobacco-derived nitrosamine on immortalized oral epithelial cells. Biochem Pharmacol 74(8), 1315-9.
Arredondo, J., Chernyavsky, A. I., and Grando, S. A. (2007). SLURP-1 and -2 in normal, immortalized and malignant oral keratinocytes. Life Sci 80(24-25), 2243-7.
Song, P., Sekhon, H. S., Lu, A., Arredondo, J., Sauer, D., Gravett, C., Mark, G. P., Grando, S. A., and Spindel, E. R. (2007). M3 muscarinic receptor antagonists inhibit small cell lung carcinoma growth and mitogen-activated protein kinase phosphorylation induced by acetylcholine secretion. Cancer Res 67(8), 3936-44. |
