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Published on: June 9, 2023
(-)‑Oleocanthal inhibits proliferation and migration by modulating Ca2+ entry through TRPC6 in breast cancer cells
R Diez-Bello1, I Jardin1, J J Lopez1
1Department of Physiology (Cellular Physiology Research Group), Institute of Molecular Pathology Biomarkers, University of Extremadura, 10003 Caceres, Spain.
Abstract:
Triple negative breast cancer is an aggressive type of cancer that does not respond to hormonal therapy and current therapeutic strategies are accompanied by side effects due to cytotoxic actions on normal tissues. Therefore, there is a need for the identification of anti-cancer compounds with negligible effects on non-tumoral cells. Here we show that (-)‑oleocanthal (OLCT), a phenolic compound isolated from olive oil, selectively impairs MDA-MB-231 cell proliferation and viability without affecting the ability of non-tumoral MCF10A cells to proliferate or their viability. Similarly, OLCT selectively impairs the ability of MDA-MB-231 cells to migrate while the ability of MCF10A to migrate was unaffected. The effect of OLCT was not exclusive for triple negative breast cancer cells as we found that OLCT also attenuate cell viability and proliferation of MCF7 cells. Our results indicate that OLCT is unable to induce Ca2+ mobilization in non-tumoral cells. By contrast, OLCT induces Ca2+ entry in MCF7 and MDA-MB-231 cells, which is impaired by TRPC6 expression silencing. We have found that MDA-MB-231 and MCF7 cells overexpress the channel TRPC6 as compared to non-tumoral MCF10A and treatment with OLCT for 24-72 h downregulates TRPC6 expression in MDA-MB-231 cells. These findings indicate that OLCT impairs the ability of breast cancer cells to proliferate and migrate via downregulation of TRPC6 channel expression while having no effect on the biology of non-tumoral breast cells.
Insights
(-)‑oleocanthal (OLCT), derived from olive oil, selectively targets triple-negative breast cancer cells, inhibiting proliferation and migration. This natural compound shows promise as a targeted therapy with minimal impact on healthy cells.
Area of Science:
- * Molecular Biology
- * Oncology
- * Pharmacology
Background:
- * Triple-negative breast cancer (TNBC) is aggressive and lacks targeted therapies, necessitating novel treatments.
- * Current therapies often cause severe side effects due to their impact on normal cells.
- * There is a critical need for anti-cancer compounds with selective toxicity towards tumor cells.
Purpose of the Study:
- * To investigate the selective anti-cancer effects of (-)‑oleocanthal (OLCT) on breast cancer cells.
- * To determine the mechanism of OLCT's action, focusing on TRPC6 channels and calcium signaling.
- * To evaluate OLCT's impact on both cancerous and non-tumoral breast cell lines.
Main Methods:
- * Cell proliferation, viability, and migration assays were performed on MDA-MB-231 (TNBC), MCF7 (ER+ breast cancer), and MCF10A (non-tumoral) cell lines.
- * Calcium (Ca2+) mobilization and TRPC6 channel expression were analyzed.
- * TRPC6 expression silencing was used to investigate its role in OLCT's mechanism.
Main Results:
- * OLCT selectively reduced proliferation and viability in MDA-MB-231 and MCF7 cells, sparing MCF10A cells.
- * OLCT inhibited MDA-MB-231 cell migration without affecting MCF10A cells.
- * OLCT induced Ca2+ entry in cancer cells via TRPC6 channels, and downregulated TRPC6 expression in MDA-MB-231 cells.
Conclusions:
- * (-)‑oleocanthal (OLCT) demonstrates selective anti-cancer properties against triple-negative and other breast cancer cells.
- * OLCT's mechanism involves the downregulation of TRPC6 channel expression, impacting cancer cell proliferation and migration.
- * OLCT represents a potential therapeutic agent for breast cancer with a favorable safety profile for non-tumoral cells.
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