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I3C and ICZ inhibit migration by suppressing the EMT process and FAK expression in breast cancer cells
Jin-Nyoung Ho1, Woojin Jun, Ryowon Choue
1Department of Medical Nutrition, Kyung Hee University, Gyeonggi-do 446-701, Republic of Korea.
Abstract:
Indole-3-carbinol (I3C) and indole[3,2-b] carbazole (ICZ) are major bioactive food components in cruciferous vegetables. Although previous studies have demonstrated the anticancer activity of I3C and ICZ in various types of cancer cells, the manner in which indole compounds regulate migration or related epithelial-to-mesenchymal transitions (EMT) has yet to be determined. In this study, we investigated the effects of I3C and ICZ on migration using breast cancer cells (MCF-7 and MDA-MB231). Pre‑treatment with I3C and ICZ significantly inhibited the migration of breast cancer cells without cytotoxicity, as measured by monolayer scratch assay. In addition, I3C and ICZ decreased vimentin (a mesenchymal marker) and focal adhesion kinase (FAK) mRNA expression, while increasing E-cadherin (an epithelial marker) expression. Matrix metalloproteinase (MMP)-2 and -9 activity was also reduced by I3C and ICZ. Taken together, we propose that I3C and ICZ pre‑treatment inhibits the migration of breast cancer cells through suppression of the EMT process and reduced MMP activity by repressing FAK expression. Our findings suggested that I3C and ICZ are potential compounds for inhibition of breast cancer cell migration.
Insights
Indole-3-carbinol (I3C) and indole[3,2-b] carbazole (ICZ) from cruciferous vegetables inhibit breast cancer cell migration. These compounds suppress epithelial-to-mesenchymal transitions (EMT) and reduce matrix metalloproteinase activity without causing cell death.
Area of Science:
- Biochemistry
- Molecular Biology
- Oncology
Background:
- Indole-3-carbinol (I3C) and indole[3,2-b] carbazole (ICZ) are bioactive compounds found in cruciferous vegetables.
- Previous research indicates I3C and ICZ possess anticancer properties against various cancer cell types.
- The impact of indole compounds on cancer cell migration and epithelial-to-mesenchymal transitions (EMT) remains incompletely understood.
Purpose of the Study:
- To investigate the effects of I3C and ICZ on the migration of breast cancer cells.
- To determine if I3C and ICZ influence the epithelial-to-mesenchymal transition (EMT) process in breast cancer cells.
- To explore the underlying molecular mechanisms by which I3C and ICZ affect cancer cell motility.
Main Methods:
- Utilized MCF-7 and MDA-MB231 breast cancer cell lines.
- Assessed cell migration using the monolayer scratch assay.
- Quantified changes in mRNA expression of key EMT markers (vimentin, E-cadherin) and focal adhesion kinase (FAK).
- Measured the activity of matrix metalloproteinases (MMP-2 and MMP-9).
Main Results:
- Pre-treatment with I3C and ICZ significantly inhibited breast cancer cell migration.
- No cytotoxic effects were observed at the tested concentrations.
- I3C and ICZ decreased vimentin and FAK mRNA expression while increasing E-cadherin expression, indicating EMT suppression.
- Reduced activity of MMP-2 and MMP-9 was observed following I3C and ICZ treatment.
Conclusions:
- I3C and ICZ effectively inhibit breast cancer cell migration.
- These indole compounds suppress cancer cell migration by inhibiting the EMT process and reducing MMP activity, partly through FAK repression.
- I3C and ICZ show potential as therapeutic or preventative agents against breast cancer metastasis.
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