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Published on: January 20, 2019
Lidocaine Suppresses Viability and Migration of Human Breast Cancer Cells: TRPM7 as a Target for Some Breast Cancer
Hengrui Liu, James P Dilger1, Jun Lin1
1Department of Anesthesiology, Health Science Center, Stony Brook University, Stony Brook, NY 11794, USA.
Background:
The local anesthetic lidocaine suppresses some cancer cell lines but the mechanism is unclear. The melastatin-like transient receptor potential 7 (TRPM7) ion channel is aberrantly expressed in some cancers and may play a role in the disease. Hence, we suggested that lidocaine affects the viability and migration of breast cancer cells by regulating TRPM7.
Methods:
We measured the effects of lidocaine on TRPM7 function in HEK293 with exogenous TRPM7 expression (HEK-M7) using whole-cell patch-clamp and fura-2AM-based quench assay. We measured the effect of lidocaine on TRPM7 function, cell viability, and migration in TRPM7 expressing human breast cancer cell lines using fura-2AM-based quench, MTT, and wound-healing assays respectively. We compared cell viability and migration of wild type HEK293 cells (WT-HEK) with HEK-M7 and wild type MDA-MB-231 (WT-231) with TRPM7 knockout MDA-MB-231 (KO-231).
Results:
Lidocaine (1-3 mM) inhibited the viability and migration of all of these breast cancer cell lines. Functional evidence for TRPM7 was confirmed in the MDA-MB-231, AU565, T47D, and MDA-MB-468 cell lines where lidocaine at 0.3-3 mM suppressed the TRPM7 function. Lidocaine preferentially suppressed viability and migration of HEK-M7 over WT-HEK and WT-231 over KO-231.
Conclusions:
Lidocaine differentially reduced the viability and migration of human breast cancer cell lines tested. TRPM7 is one of the potential targets for the effects of lidocaine on viability and migration in MDA-MB-231, AU565, T47D, and MDA-MB-468.
Insights
Lidocaine inhibits breast cancer cell viability and migration by targeting the TRPM7 ion channel. This study reveals TRPM7 as a potential therapeutic target for breast cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- The local anesthetic lidocaine exhibits inhibitory effects on certain cancer cell lines, but the underlying mechanisms remain unclear.
- Aberrant expression of the melastatin-like transient receptor potential 7 (TRPM7) ion channel is observed in various cancers, suggesting its potential role in disease progression.
- This study investigates the hypothesis that lidocaine influences breast cancer cell viability and migration by modulating TRPM7 activity.
Purpose of the Study:
- To elucidate the mechanism by which lidocaine affects breast cancer cell viability and migration.
- To determine the role of the TRPM7 ion channel in mediating the effects of lidocaine on breast cancer cells.
- To assess lidocaine's impact on TRPM7 function and its downstream effects on cancer cell behavior.
Main Methods:
- Whole-cell patch-clamp and fura-2AM-based quench assays were employed to measure TRPM7 channel function in response to lidocaine.
- Cell viability was assessed using MTT assays, and cell migration was evaluated through wound-healing assays in TRPM7-expressing breast cancer cell lines.
- Comparative analyses of cell viability and migration were performed between wild-type and TRPM7 knockout/exogenously expressed cell lines (HEK293 and MDA-MB-231).
Main Results:
- Lidocaine (1-3 mM) significantly inhibited the viability and migration of all tested human breast cancer cell lines.
- Functional TRPM7 activity was confirmed in MDA-MB-231, AU565, T47D, and MDA-MB-468 cell lines, with lidocaine (0.3-3 mM) suppressing this activity.
- Lidocaine demonstrated a preferential suppression of viability and migration in cells with TRPM7 expression (HEK-M7 vs. WT-HEK; WT-231 vs. KO-231).
Conclusions:
- Lidocaine exhibits differential effects in reducing the viability and migration of various human breast cancer cell lines.
- TRPM7 is identified as a key molecular target mediating the observed effects of lidocaine on cancer cell viability and migration in specific breast cancer subtypes.
- These findings suggest TRPM7 as a potential therapeutic target for interventions involving lidocaine in breast cancer treatment.
