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      Transient Receptor Potential Cation Channels in Cancer Therapy

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          Abstract

          In mammals, the transient receptor potential (TRP) channels family consists of six different families, namely TRPC (canonical), TRPV (vanilloid), TRPM (melastatin), TRPML (mucolipin), TRPP (polycystin), and TRPA (ankyrin), that are strictly connected with cancer cell proliferation, differentiation, cell death, angiogenesis, migration, and invasion. Changes in TRP channels’ expression and function have been found to regulate cell proliferation and resistance or sensitivity of cancer cells to apoptotic-induced cell death, resulting in cancer-promoting effects or resistance to chemotherapy treatments. This review summarizes the data reported so far on the effect of targeting TRP channels in different types of cancer by using multiple TRP-specific agonists, antagonists alone, or in combination with classic chemotherapeutic agents, microRNA specifically targeting the TRP channels, and so forth, and the in vitro and in vivo feasibility evaluated in experimental models and in cancer patients. Considerable efforts have been made to fight cancer cells, and therapies targeting TRP channels seem to be the most promising strategy. However, more in-depth investigations are required to completely understand the role of TRP channels in cancer in order to design new, more specific, and valuable pharmacological tools.

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          Most cited references112

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          Molecular mechanism of TRP channels.

          Jie Zheng (2013)
          Transient receptor potential (TRP) channels are cellular sensors for a wide spectrum of physical and chemical stimuli. They are involved in the formation of sight, hearing, touch, smell, taste, temperature, and pain sensation. TRP channels also play fundamental roles in cell signaling and allow the host cell to respond to benign or harmful environmental changes. As TRP channel activation is controlled by very diverse processes and, in many cases, exhibits complex polymodal properties, understanding how each TRP channel responds to its unique forms of activation energy is both crucial and challenging. The past two decades witnessed significant advances in understanding the molecular mechanisms that underlie TRP channels activation. This review focuses on our current understanding of the molecular determinants for TRP channel activation.
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            Trp-p8, a novel prostate-specific gene, is up-regulated in prostate cancer and other malignancies and shares high homology with transient receptor potential calcium channel proteins.

            We have identified and cloned a novel gene, trp-p8, by screening a prostate-specific subtracted cDNA library. The 5694-bp cDNA has a 3312-bp open reading frame, which codes for a 1104 amino acid putative protein with seven transmembrane domains. The predicted protein revealed significant homology with the transient receptor potential (trp) family of Ca(2+) channel proteins. Northern blot analysis indicated that trp-p8 expression within normal human tissues is mostly restricted to prostate epithelial cells. In situ hybridization analysis showed that trp-p8 mRNA expression was at moderate levels in normal prostate tissue and appears to be elevated in prostate cancer. Notably, trp-p8 mRNA was also expressed in a number of nonprostatic primary tumors of breast, colon, lung, and skin origin, whereas transcripts encoding trp-p8 were hardly detected or not detected in the corresponding normal human tissues.
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              Tranilast: a review of its therapeutic applications.

              Tranilast (N-[3',4'-dimethoxycinnamoyl]-anthranilic acid) is an analog of a tryptophan metabolite. Initially, tranilast was identified as an anti-allergic agent, and used in the treatment of inflammatory diseases, such as bronchial asthma, atypical dermatitis, allergic conjunctivitis, keloids and hypertrophic scars. Subsequently, the results showed that it could be also effective in the management of a wide range of conditions. The beneficial effects of tranilast have also been seen in a variety of disease states, such as fibrosis, proliferative disorders, cancer, cardiovascular problems, autoimmune disorders, ocular diseases, diabetes and renal diseases. Moreover, several trials have shown that it has very low adverse effects and it is generally well tolerated by patients. In this review, we have attempted to accurately summarize previously published studies relating to the use of tranilast for a range of disorders and discuss the drug's possible mode of action. The major mode of the drug's efficacy appears to be the suppression of the expression and/or action of the TGF-β pathway, but the drug affects other factors as well. The findings presented in this review demonstrate the potential of tranilast for the control of a vast array of pathological situations, furthermore, it is a prescribed drug without severe side effects.
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                Author and article information

                Journal
                Med Sci (Basel)
                Med Sci (Basel)
                medsci
                Medical Sciences
                MDPI
                2076-3271
                30 November 2019
                December 2019
                : 7
                : 12
                : 108
                Affiliations
                [1 ]School of Pharmacy, University of Camerino, via Madonna delle Carceri 9, 62032 Camerino (MC), Italy; federica.maggi@ 123456uniroma1.it (F.M.); mariabeatrice.morelli@ 123456unicam.it (M.B.M.); oliviero.marinelli@ 123456unicam.it (O.M.)
                [2 ]Department of Molecular Medicine, Sapienza University, Viale Regina Elena 324, 00161 Rome (RM), Italy
                [3 ]Medical Oncology Unit, Hospital of Macerata, Via Santa Lucia 2, 62100 Macerata (MC), Italy; mattymo@ 123456alice.it
                [4 ]School of Biosciences and Veterinary Medicine, University of Camerino, via Madonna delle Carceri 9, 62032 Camerino (MC), Italy
                Author notes
                [* ]Correspondence: giorgio.santoni@ 123456unicam.it ; Tel.: +39-0737403319; Fax: +39-0737403325
                Author information
                https://orcid.org/0000-0002-4614-5649
                Article
                medsci-07-00108
                10.3390/medsci7120108
                6950741
                31801263
                4ab2b0bf-bf13-42e8-a172-e9f0805d9561
                © 2019 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 24 September 2019
                : 26 November 2019
                Categories
                Review

                transient receptor potential channels,tumor progression,chemotherapy resistance

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