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Published on: June 9, 2023
Carvacrol affects breast cancer cells through TRPM7 mediated cell cycle regulation
Leilei Li1, Liang He1, Yalei Wu1
1Department of Thyroid and Breast Surgery, Luoyang Central Hospital Affiliated to Zhengzhou University, 471009, China.
Abstract:
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.
Insights
Carvacrol, a natural compound, inhibits breast cancer cell growth and induces apoptosis by regulating the cell cycle via the transient receptor potential melastatin-like 7 (TRPM7) channel.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Breast cancer is a leading cause of cancer death in women, necessitating novel therapeutic strategies.
- Transient receptor potential melastatin-like 7 (TRPM7) channels are implicated in cancer progression.
- Carvacrol, a natural TRPM7 inhibitor, shows potential anti-cancer activity.
Purpose of the Study:
- To investigate the anti-cancer effects of carvacrol on breast cancer cells.
- To determine if carvacrol's effects are mediated through TRPM7-dependent cell cycle regulation.
Main Methods:
- Cell viability (CCK-8 assay) and apoptosis (ELISA) were assessed in multiple breast cancer cell lines.
- TRPM7 function was evaluated using western blotting, patch-clamp, and fura-2 quench assays.
- Cell cycle distribution and regulatory protein expression were analyzed by flow cytometry and western blotting, with TRPM7 knockdown experiments.
Main Results:
- Carvacrol inhibited breast cancer cell viability with varying potency; MDA-MB-231 cells were most sensitive.
- Apoptosis was significantly induced at concentrations above 200 μM.
- Carvacrol suppressed TRPM7 channel activity and altered cell cycle progression (G1/G0 arrest) by regulating cyclin proteins in MDA-MB-231 cells.
- These carvacrol-induced effects were abrogated by TRPM7 knockdown.
Conclusions:
- Carvacrol exhibits anti-cancer properties against breast cancer cells.
- The TRPM7 pathway is a key pharmacological target for carvacrol's anti-cancer effects, involving cell cycle regulation.
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