Department of Thyroid and Breast Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, 471009, China.
Department of Breast Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, 471009, China.
Life Sci. 2021 Feb 1;266:118894. doi: 10.1016/j.lfs.2020.118894. Epub 2020 Dec 10.
As the most prevalent cancer for females, breast cancer is also the second most popular cancer type overall. More efforts are needed to research new drugs and combination therapies for this disease. A naturally derived transient receptor potential melastatin-like 7 channel (TRPM7) inhibitor, carvacrol, was found to have anti-cancer potentials. We hypothesized that carvacrol affects breast cancer cells through TRPM7 mediated cell cycle regulation. Cell viability and apoptosis of breast cancer cell lines BT-483, BT-474, MCF-7, MDA-MB-231, and MDA-MB-453 were determined using the CCK-8 assay and ELISA respectively. TRPM7 in MDA-MB-231, MCF-7 was knocked down. Functional TRPM7 in MDA-MB-231, MCF-7, and HEK293 cells were tested with western blotting, patch-clamp, and fura-2 quench assay. The cell cycle and the regulatory proteins were determined by flow cytometry and western blotting. Results showed that carvacrol inhibited the viability of breast cancer cells with different potency. At 200 μM, MDA-MB-231 was the most sensitive, and MCF-7 was the least sensitive. At >200 μM, the apoptosis was dramatically induced. Carvacrol inhibited TRPM7 functions in MDA-MB-231, MCF-7, and HEK293. Carvacrol at 200 μM increased cells in the G1/G0 phase and decreased cells in the S and G2/M phase by regulating some cyclin proteins in MDA-MB-231. These effects were blocked by the knockdown of TRPM7. This study demonstrated that carvacrol suppresses breast cancer cells by cell cycle regulation and the TRPM7 pathway is one of the pharmacological mechanisms.
作为女性最常见的癌症，乳腺癌也是总体上第二大常见的癌症类型。需要更多的努力来研究这种疾病的新药和联合治疗方法。一种天然衍生的瞬时受体电位 melastatin 样 7 通道（TRPM7）抑制剂香芹酚被发现具有抗癌潜力。我们假设香芹酚通过 TRPM7 介导的细胞周期调节影响乳腺癌细胞。使用 CCK-8 测定法和 ELISA 分别测定乳腺癌细胞系 BT-483、BT-474、MCF-7、MDA-MB-231 和 MDA-MB-453 的细胞活力和细胞凋亡。敲低 MDA-MB-231、MCF-7 中的 TRPM7。使用 Western blot、膜片钳和 fura-2 猝灭测定法测试 MDA-MB-231、MCF-7 和 HEK293 细胞中的功能性 TRPM7。通过流式细胞术和 Western blot 测定细胞周期和调节蛋白。结果表明，香芹酚以不同的效力抑制乳腺癌细胞的活力。在 200μM 时，MDA-MB-231 最敏感，而 MCF-7 最不敏感。在 >200μM 时，凋亡明显诱导。香芹酚抑制 MDA-MB-231、MCF-7 和 HEK293 中的 TRPM7 功能。香芹酚在 200μM 时通过调节 MDA-MB-231 中的一些细胞周期蛋白，增加 G1/G0 期的细胞，减少 S 和 G2/M 期的细胞。这些作用被 TRPM7 的敲低阻断。这项研究表明，香芹酚通过细胞周期调节抑制乳腺癌细胞，而 TRPM7 途径是其中一种药理学机制。
