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Published on: June 9, 2023
Phytochemicals potently inhibit migration of metastatic breast cancer cells
Stephanie Lemmo Ham1, Samila Nasrollahi, Kush N Shah
1Department of Biomedical Engineering, The University of Akron, Akron, Ohio 44325, USA. tavana@uakron.edu.
Abstract:
Cell migration is a major process that drives metastatic progression of cancers, the major cause of cancer death. Existing chemotherapeutic drugs have limited efficacy to prevent and/or treat metastasis, emphasizing the need for new treatments. We focus on triple negative breast cancer (TNBC), the subtype of breast cancer with worst prognosis and no standard chemotherapy protocols. Here we demonstrate that a group of natural compounds, known as phytochemicals, effectively block migration of metastatic TNBC cells. Using a novel cell micropatterning technology, we generate consistent migration niches in standard 96-well plates where each well contains a cell-excluded gap within a uniform monolayer of cells. Over time, cells migrate into and occupy the gap. Treating TNBC cells with non-toxic concentrations of phytochemicals significantly blocks motility of cells. Using a molecular analysis approach, we show that anti-migratory property of phytochemicals is partly due to their inhibitory effects on phosphorylation of ERK1/2. This study provides a framework for future studies to understand molecular targets of phytochemicals and evaluate their effectiveness in inhibiting metastasis in animal models of cancer.
Insights
Phytochemicals effectively block the migration of triple-negative breast cancer (TNBC) cells. This natural compound approach offers a promising new strategy for preventing cancer metastasis and improving patient outcomes.
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- Cell migration is a critical driver of cancer metastasis, the primary cause of cancer-related mortality.
- Triple-negative breast cancer (TNBC) presents a poor prognosis with limited therapeutic options for metastasis.
- There is an urgent need for novel therapeutic strategies to combat cancer metastasis.
Purpose of the Study:
- To investigate the efficacy of phytochemicals in inhibiting the migration of triple-negative breast cancer (TNBC) cells.
- To explore the molecular mechanisms underlying the anti-migratory effects of phytochemicals.
- To establish a novel cell micropatterning assay for evaluating cell migration inhibitors.
Main Methods:
- Utilized a novel cell micropatterning technology to create consistent migration niches in 96-well plates.
- Assessed the effect of non-toxic concentrations of phytochemicals on TNBC cell migration into defined gaps.
- Employed molecular analysis to investigate the impact of phytochemicals on signaling pathways, specifically ERK1/2 phosphorylation.
Main Results:
- Phytochemicals significantly inhibited the motility of metastatic TNBC cells at non-toxic concentrations.
- The anti-migratory effect of phytochemicals was partly attributed to the inhibition of ERK1/2 phosphorylation.
- The developed cell micropatterning assay provided a reproducible platform for migration studies.
Conclusions:
- Phytochemicals demonstrate significant potential as anti-metastatic agents for triple-negative breast cancer.
- Inhibition of ERK1/2 phosphorylation is a key mechanism by which phytochemicals impede cancer cell migration.
- This research provides a foundation for developing phytochemical-based therapies and further investigation in preclinical cancer models.
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