fa Differential expression of organic cation transporter OCT-3 in oral premalignant and malignant lesions: potential implications in the antineoplastic effects of metformin بیماری های دهان Oral Medicine پژوهشي Research <p> <strong>Background</strong></p><p>  Recent evidence indicates that metformin, a biguanide used as first-line treatment for type 2 diabetes, prevents the conversion of carcinogen-induced oral dysplasias into head and neck squamous cell carcinomas (HNSCC), most likely by inhibiting mammalian target of rapamycin complex 1 (mTORC1) oncogenic signaling. Whether metformin acts directly at the primary tumor site or indirectly by modulating hormonal secretion from extratumoral organs remains unknown. As organic cation transporters (OCT) belonging to the solute carrier 22A gene family, including OCT-1, OCT-2, and OCT-3, mediate metformin uptake and activity, it is critical to define what role they play in the antineoplastic activity of metformin. </p><p> <strong>Methods</strong></p><p>  Immunohistochemical and immunoblotting techniques were used in normal, dysplastic and HNSCC tissues, and HNSCC cell lines, respectively, to determine OCTs expression levels. </p><p> <strong>Results</strong></p><p>  We report that only OCT-3 was highly expressed in a number of HNSCC cell lines, oral epithelial dysplasias, and well to moderately differentiated HNSCC. Indeed, inhibition of OCT-3 expression and activity in HNSCC cells prevented metformin-induced AMP-activated protein kinase activation and mTORC1 pathway inhibition. Moreover, in oral dysplasias, high OCT-3 expression localized to epithelial compartments where mTORC1 signaling was also upregulated suggestive of a potential local effect of metformin. </p><p> <strong>Conclusions </strong></p><p> The concept of using metformin as a chemopreventive agent to control head and neck carcinogenesis is promising. Further work is warranted to elucidate largely unexplored mechanisms of metformin uptake and pharmacologic action that may ultimately influence the selection of the most suitable patients who can benefit from metformin in head and neck cancer chemoprevention. </p><hr><p></p><p> <strong>Source: </strong>Journal of Oral Pathology & Medicine</p><p><a href="http://onlinelibrary.wiley.com/doi/10.1111/j.1600-0714.2012.01196.x/abstract" target="_blank"><font color="#0000ff"> Full Text</font></a></p> AMPK;metformin;oral cancer;oral precancer;organic cation transporters 0 0 http://idai.ir/browse.php?a_code=A-10-32-2244&slc_lang=fa&sid=1 Harsh Patel 100319475328460010596 100319475328460010596 No Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD, USA Rania H. Younis 100319475328460010597 100319475328460010597 No Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD, USA Robert A.Ord 100319475328460010598 100319475328460010598 No Department of Oral-Maxillofacial Surgery, University of Maryland School of Dentistry, Baltimore, MD, USA John R. Basile 100319475328460010599 100319475328460010599 No Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD, USA/University of Maryland Greenebaum Cancer Center, Baltimore, MD, USA Abraham Schneider aschneider@umaryland.edu 100319475328460010600 100319475328460010600 Yes Department of Oncology and Diagnostic Sciences, University of Maryland School of Dentistry, Baltimore, MD, USA/University of Maryland Greenebaum Cancer Center, Baltimore, MD, USA