Department of Stomatology, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Institute of Neuroscience, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China; Key Laboratory of Neurogenetics and Channelopathies of the Ministry of Education of China, Guangzhou, China.
Department of Prevention and Health-Care, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China.
J Oral Biosci. 2024 Jun;66(2):430-438. doi: 10.1016/j.job.2024.03.002. Epub 2024 Mar 6.
To elucidate the association between the anticancer activities of piperlongumine (PL) and its potential target, transient receptor potential melastatin 7 channel (TRPM7), in oral squamous cell carcinoma (OSCC).
The expression levels and electrical characteristics of TRPM7 as well as cell viability in response to various PL treatments were investigated in the OSCC cell line Cal27.
PL treatment resulted in a concentration- and time-dependent reduction in TRPM7 mRNA and protein expression in Cal27 cells. Furthermore, PL treatment inhibited TRPM7-like rectifying currents in Cal27 cells; however, this inhibition was less effective than that of the TRPM7 antagonist waixenicin A. Rapid perfusion and washout experiments revealed an immediate inhibitory effect of PL on TRPM7-like currents. The antagonistic effect of PL occurred within 1 min and was not completely reversed following washout. Notably, the extracellular Ca concentration still influenced PL-induced changes in the TRPM7-like current, indicating that PL can directly but gently antagonize the TRPM7 channel. Functional changes in TRPM7 correlated with the observed antiproliferative and cytotoxic effects of PL in Cal27 cells.
These findings suggest that PL exhibits potent inhibitory effects on TRPM7 and exerts its anti-cancer effects by downregulating TRPM7 expression and antagonizing channel currents.
阐明胡椒碱（PL）的抗癌活性与其潜在靶标瞬时受体电位 melastatin 7 通道（TRPM7）在口腔鳞状细胞癌（OSCC）中的关联。
在 OSCC 细胞系 Cal27 中研究了 TRPM7 的表达水平和电特性以及对各种 PL 处理的细胞活力。
PL 处理导致 Cal27 细胞中 TRPM7 mRNA 和蛋白表达呈浓度和时间依赖性降低。此外，PL 处理抑制了 Cal27 细胞中的 TRPM7 样整流电流；然而，这种抑制作用不如 TRPM7 拮抗剂 Waixenicin A 有效。快速灌注和冲洗实验显示 PL 对 TRPM7 样电流具有即刻抑制作用。PL 的拮抗作用在 1 分钟内发生，冲洗后并未完全逆转。值得注意的是，细胞外 Ca 浓度仍影响 PL 诱导的 TRPM7 样电流变化，表明 PL 可直接但温和地拮抗 TRPM7 通道。TRPM7 的功能变化与在 Cal27 细胞中观察到的 PL 抗增殖和细胞毒性作用相关。
这些发现表明，PL 对 TRPM7 具有强大的抑制作用，并通过下调 TRPM7 表达和拮抗通道电流发挥其抗癌作用。
