CCK8 and flow cytometry were used to detect the proliferation and cell cycle, while transwell assay was used to detect migration and invasion. Methods: The expression of TRPV1 in GC cells and tissues was detected by qPCR, immunohistochemistry, western blot analysis and immunofluorescence. We sought to determine their role in the development of GC and to elucidate the underlying molecular mechanisms. New ligands specific to the TRPV subfamily may be useful for the design of medicines as in the study of TRP channels biology.īackground: Although the aberrant expression and function of most Ca²⁺-permeable channels are known to promote gastrointestinal tumors, the association of transient receptor potential vanilloid receptor 1(TRPV1) channels and gastric cancer (GC) has not been explored so far. We showed that the removal of one of three side chains or double bonds in the other side chains in urupocidin A led to a decrease of the inhibitory activities. Two semi-synthetic urupocidin A derivatives were also obtained and tested against TRP (Transient Receptor Potential) receptors that allowed us to collect some data concerning the structure-activity relationship in this series of compounds. Moreover, monanchomycalin B and urupocidin A are the first samples of marine alkaloids affecting the TRPV2 receptor. Monanchomycalin B is the most active among all published marine alkaloids (EC50 6.02, 2.84, and 3.25 μM for TRPV1, TRPV2, and TRPV3, correspondingly). We found that they act as inhibitors of the TRPV1, TRPV2, and TRPV3 channels, but are inactive against the TRPA1 receptor. Monanchomycalin B and urupocidin A were isolated from the marine sponge Monanchora pulchra. Marine sponges contain a variety of low-molecular-weight compounds including guanidine alkaloids possessing different biological activities. Furthermore, the potency and specificity of these agents will be discussed as well as the development of new strategies targeting TRP channels in cancer. Here we describe the effects of such TRP modulators on TRP activity and cancer cell phenotype. Moreover, pharmacological modulation of TRP activity in cancer cells is systematically linked to the effect on cancerous processes (proliferation, survival, migration, invasion, sensitivity to chemotherapeutic drugs). Pharmacological modulators are used to characterize the functional implications of TRP channels in whole-cell membrane currents, resting membrane potential regulation and intracellular Ca(2+) signaling. Among the TRP superfamily, TRPC, TRPV, TRPM and TRPA1 have been shown to play a role in many cancer types including breast, digestive, gliomas, head and neck, lung, and prostate cancers. Moreover, these proteins are involved in many cancerous processes including cell proliferation, apoptosis, migration, invasion as well as resistance to chemotherapy. Indeed, there is growing evidence that TRP channels expression is altered in cancer tissues in comparison to the normal ones. However, dysfunction in channel expression and/or activity can be linked to human diseases like cancer. Physiologically, TRP channels are responsible for cation entry (Ca(2+), Na(+), Mg(2+) ) in many mammalian cells and regulate a large number of cellular functions. The aim of this review is to address the recent advances regarding the use of pharmacological agents to target the Transient Receptor Potential (TRP) channels in cancer and their potential application in therapeutics.
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