Transient receptor potential melastatin 8 (TRPM8) is a calcium ion-permeable cation channel that is used as a prognostic marker and therapeutic target for different tumor types. To identify natural selective TRPM8 antagonists, we tested 158 traditional Chinese medicine (TCM) compounds for the ability to inhibit TRPM8. Calcium mobilization assays were used to evaluate the 158 TCM compound components in HEK293 cells stably expressing TRPM8. An identified putative TRPM8 antagonist, sesamin, was further evaluated. Publicly available cancer OMICS data were used to explore the expression of TRPM8, its gene regulatory network, and the survival of patients with prostate adenocarcinoma (PRAD). The cytotoxicity and specificity of sesamin to TRPM8 were tested in HEK293/TRPM8 cells. The effect of sesamin on cell proliferation in PRAD cell lines was assessed. Sesamin selectively inhibited TRPM8 in HEK293/TRPM8 cells (IC50: 9.78 μM), and a molecular docking study confirmed the binding of sesamin to TRPM8. TRPM8 was highly overexpressed in PRAD, and high TRPM8 expression was associated with poor survival of PRAD patients. Functional network analysis suggested that TRPM8 has key effects on proliferation, survival, and invasion of prostate cancer cells. Cell proliferation assays supported these findings and showed that sesamin inhibited the proliferation of PRAD cell lines DU145 and LNCaP cells. These data revealed that abnormal TRPM8 expression is associated with PRAD and that sesamin is a new anti-PRAD candidate drug, exerting inhibitory effects on TRPM8.

中文翻译：

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鉴定天然化合物芝麻素为新型TRPM8拮抗剂，对前列腺腺癌具有抑制作用。

瞬时受体电位褪黑素8（TRPM8）是钙离子可渗透的阳离子通道，可用作不同肿瘤类型的预后标志物和治疗靶标。为了鉴定天然的选择性TRPM8拮抗剂，我们测试了158种中药（TCM）化合物抑制TRPM8的能力。钙动员试验用于评估稳定表达TRPM8的HEK293细胞中的158种中药化合物成分。鉴定的推定TRPM8拮抗剂芝麻素被进一步评估。公开的癌症OMICS数据用于探讨TRPM8的表达，其基因调控网络以及前列腺腺癌（PRAD）患者的生存。在HEK293 / TRPM8细胞中测试了芝麻素对TRPM8的细胞毒性和特异性。评估了芝麻素对PRAD细胞系中细胞增殖的影响。芝麻素选择性抑制HEK293 / TRPM8细胞中的TRPM8（IC50：9.78μM），分子对接研究证实了芝麻素与TRPM8的结合。TRPM8在PRAD中高度过表达，而高TRPM8表达与PRAD患者存活率低有关。功能网络分析表明，TRPM8对前列腺癌细胞的增殖，存活和侵袭具有关键作用。细胞增殖测定支持了这些发现，并表明芝麻素抑制了PRAD细胞系DU145和LNCaP细胞的增殖。这些数据表明TRPM8的异常表达与PRAD有关，而芝麻素是一种新的抗PRAD候选药物，对TRPM8具有抑制作用。TRPM8在PRAD中高度过表达，而高TRPM8表达与PRAD患者存活率低有关。功能网络分析表明，TRPM8对前列腺癌细胞的增殖，存活和侵袭具有关键作用。细胞增殖测定支持了这些发现，并表明芝麻素抑制了PRAD细胞系DU145和LNCaP细胞的增殖。这些数据表明TRPM8的异常表达与PRAD有关，而芝麻素是一种新的抗PRAD候选药物，对TRPM8具有抑制作用。TRPM8在PRAD中高度过表达，而高TRPM8表达与PRAD患者存活率低有关。功能网络分析表明，TRPM8对前列腺癌细胞的增殖，存活和侵袭具有关键作用。细胞增殖测定支持了这些发现，并表明芝麻素抑制了PRAD细胞系DU145和LNCaP细胞的增殖。这些数据表明TRPM8的异常表达与PRAD有关，而芝麻素是一种新的抗PRAD候选药物，对TRPM8具有抑制作用。细胞增殖测定支持了这些发现，并表明芝麻素抑制了PRAD细胞系DU145和LNCaP细胞的增殖。这些数据表明TRPM8的异常表达与PRAD有关，而芝麻素是一种新的抗PRAD候选药物，对TRPM8具有抑制作用。细胞增殖测定支持了这些发现，并表明芝麻素抑制了PRAD细胞系DU145和LNCaP细胞的增殖。这些数据表明TRPM8的异常表达与PRAD有关，而芝麻素是一种新的抗PRAD候选药物，对TRPM8具有抑制作用。