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Published on: June 19, 2021
Zebrafish embryo extracts enhance 5-FU anti-cancer effects upon breast cancer cells
S Proietti1, A Cucina, A Catizone
1Department of Surgery "Pietro Valdoni", Sapienza University of Rome, Rome, Italy. mariano.bizzarri@uniroma1.it.
Objective:
The inhibition of the metastatic capability of cancer cells is a pivotal aim of current anticancer strategies. We investigated herein the anti-migrating and anti-invasive properties of Zebrafish embryo extracts (SL) - an integrative formula comprising morphogenetic factors extracted from zebrafish embryos - alone or in association with 5-Fluoro-Uracil (5-FU), when added to metastatic breast cancer cells (MDA-MB-231) and in normal epithelial breast cells (MCF10A) committed toward an inflammatory phenotype upon TGF-β1 stimulation.
Materials And Methods:
Invasiveness, migrating capability, cytoskeleton architecture and related molecular factors involved in the epithelial-mesenchymal transition were studied after treatment with 5-FU, with and without SL.
Results:
Remarkably, in both circumstances, embryo extracts amplify the migratory inhibition triggered by the anticancer drug 5-Fu. The fact that such an effect is noticed in normal as well as in cancerous cells suggests that the critical target of embryo extracts is specifically represented by the migrating/invasive phenotype. However, while 5-FU was unable in antagonizing the invasiveness of cancerous cells, the association with SL can significantly impair the invasive capability of tumor cells. These findings are noticeably associated with the reversion of the EMT phenotype in SL-treated cells, as documented by the contemporary downregulation of TCTP and some EMT-related molecular effectors, like α-SMA and Vimentin.
Conclusions:
Embryo fish extracts significantly counteract the migrating and invasive phenotype of cancerous and inflammatory breast cells treated with the chemotherapeutic drug 5-FU. The availability of a compound able to amplify 5-Fu activity while significantly hampering the invasive phenotype of breast cancer should provide invaluable benefits, namely if we consider that this compound is substantially deprived of side-effects.
Insights
Zebrafish embryo extracts (SL) enhance the anti-migratory effects of 5-Fluorouracil (5-FU) in breast cancer cells. SL also significantly reduces tumor cell invasiveness, offering a potential side-effect-free therapeutic strategy.
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- Cancer metastasis is a primary challenge in oncology.
- Targeting cancer cell migration and invasion is crucial for effective treatment.
- Zebrafish embryo extracts (SL) are being explored for their therapeutic potential.
Purpose of the Study:
- To investigate the anti-migrating and anti-invasive properties of Zebrafish embryo extracts (SL).
- To evaluate the synergistic effects of SL with 5-Fluorouracil (5-FU) on breast cancer cells.
- To assess the impact of SL on normal and cancerous breast cells, including those with an inflammatory phenotype.
Main Methods:
- Treatment of metastatic breast cancer cells (MDA-MB-231) and normal breast cells (MCF10A) with 5-FU alone or in combination with SL.
- Analysis of cell invasiveness, migration, cytoskeleton, and epithelial-mesenchymal transition (EMT) markers.
- Molecular analysis including TCTP, α-SMA, and Vimentin expression.
Main Results:
- SL significantly amplifies the migratory inhibition induced by 5-FU in both normal and cancerous breast cells.
- While 5-FU alone was ineffective against cancer cell invasiveness, the combination with SL significantly impaired it.
- SL treatment led to the reversion of the EMT phenotype, evidenced by downregulation of TCTP, α-SMA, and Vimentin.
Conclusions:
- Zebrafish embryo extracts (SL) effectively counteract the migrating and invasive phenotype of breast cancer cells, especially when combined with 5-FU.
- SL enhances the efficacy of 5-FU and significantly reduces breast cancer cell invasiveness.
- SL presents a promising therapeutic agent with minimal side effects for breast cancer treatment.
