Neuroscience Research Center, Suleyman Demirel University, Isparta, Turkey; Department of Biophysics, Faculty of Mediciene, Suleyman Demirel University, Isparta, Turkey.
Anatomy, Department of Medicine, University of Fribourg, Route Albert-Gockel 1, Fribourg, Switzerland.
Redox Biol. 2018 Apr;14:439-449. doi: 10.1016/j.redox.2017.10.009. Epub 2017 Oct 12.
Menthol is a naturally occurring monoterpene alcohol possessing remarkable biological properties including antipruritic, analgesic, antiseptic, anti-inflammatory and cooling effects. Here, we examined the menthol-evoked Ca signals in breast and prostate cancer cell lines. The effect of menthol (50-500µM) was predicted to be mediated by the transient receptor potential ion channel melastatin subtype 8 (TRPM8). However, the intensity of menthol-evoked Ca signals did not correlate with the expression levels of TRPM8 in breast and prostate cancer cells indicating a TRPM8-independent signaling pathway. Menthol-evoked Ca signals were analyzed in detail in Du 145 prostate cancer cells, as well as in CRISPR/Cas9 TRPM8-knockout Du 145 cells. Menthol (500µM) induced Ca oscillations in both cell lines, thus independent of TRPM8, which were however dependent on the production of inositol trisphosphate. Results based on pharmacological tools point to an involvement of the purinergic pathway in menthol-evoked Ca responses. Finally, menthol (50-500µM) decreased cell viability and induced oxidative stress independently of the presence of TRPM8 channels, despite that temperature-evoked TRPM8-mediated inward currents were significantly decreased in TRPM8-knockout Du 145 cells compared to wild type Du 145 cells.
薄荷醇是一种天然存在的单萜醇，具有显著的生物学特性，包括止痒、镇痛、防腐、抗炎和冷却作用。在这里，我们研究了薄荷醇在乳腺癌和前列腺癌细胞系中引起的 Ca 信号。薄荷醇（50-500µM）的作用预计是由瞬时受体电位离子通道 melastatin 亚型 8（TRPM8）介导的。然而，薄荷醇引起的 Ca 信号强度与乳腺癌和前列腺癌细胞中 TRPM8 的表达水平无关，表明存在 TRPM8 非依赖性信号通路。我们详细分析了 Du 145 前列腺癌细胞以及 CRISPR/Cas9 TRPM8 敲除 Du 145 细胞中的薄荷醇诱导的 Ca 信号。薄荷醇（500µM）在这两种细胞系中均诱导 Ca 振荡，因此独立于 TRPM8，而 TRPM8 依赖于三磷酸肌醇的产生。基于药理学工具的结果表明，嘌呤能途径参与了薄荷醇诱导的 Ca 反应。最后，尽管温度诱导的 TRPM8 介导的内向电流在 TRPM8 敲除 Du 145 细胞中明显低于野生型 Du 145 细胞，但薄荷醇（50-500µM）独立于 TRPM8 通道降低细胞活力并诱导氧化应激。
