Carvacrol affects breast cancer cells through TRPM7 mediated cell cycle regulation
Carvacrol affects breast cancer cells through TRPM7 mediated cell cycle regulation
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DOI：
10.1016/j.lfs.2020.118894
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发表时间：
2021-02-01
期刊：
影响因子：
6.1
通讯作者：
Zhang, Yanwu
中科院分区：
文献类型：
--
作者：
Li, Leilei;He, Liang;Zhang, Yanwu
作为女性最常见的癌症，乳腺癌也是第二大最受欢迎的癌症类型。需要更多的努力来研究这种疾病的新药物和联合疗法。天然来源的瞬时受体电位类褪黑激素7通道（TRPM 7）抑制剂香芹酚被发现具有抗癌潜力。我们推测香芹酚通过TRPM 7介导的细胞周期调控作用于乳腺癌细胞。分别用CCK-8法和ELISA法检测乳腺癌细胞系BT-483、BT-474、MCF-7、MDA-MB-231和MDA-MB-453的细胞活力和凋亡。MDA-MB-231、MCF-7中的TRPM 7被敲除。用蛋白质印迹、膜片钳和fura-2淬灭测定法测试MDA-MB-231、MCF-7和HEK 293细胞中的功能性TRPM 7。流式细胞术和Western blotting检测细胞周期和调控蛋白。结果表明，香芹酚对乳腺癌细胞活力有不同程度的抑制作用。在200 μ M时，MDA-MB-231最敏感，MCF-7最不敏感。在>200 μ M时，细胞凋亡被显著诱导。香芹酚抑制MDA-MB-231、MCF-7和HEK 293中的TRPM 7功能。200 μ M的香芹酚通过调节MDA-MB-231中的一些细胞周期蛋白增加G1/G 0期细胞，减少S和G2/M期细胞。这些作用被TRPM 7的敲低所阻断。本研究表明香芹酚通过细胞周期调控抑制乳腺癌细胞生长，TRPM 7通路是其药理机制之一。
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 mu M, MDA-MB-231 was the most sensitive, and MCF-7 was the least sensitive. At >200 mu M, the apoptosis was dramatically induced. Carvacrol inhibited TRPM7 functions in MDA-MB-231, MCF-7, and HEK293. Carvacrol at 200 mu M 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.