Carvacrol affects breast cancer cells through TRPM7 mediated cell cycle regulation

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.