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Steviol glycosides affect functional properties and macromolecular expression of breast cancer cells
Christos Velesiotis1, Marinos Kanellakis1, Demitrios H Vynios1
1Biochemistry, Biochemical Analysis & Matrix Pathobiochemistry Research Group, Department of Chemistry, University of Patras, Patras, Greece.
Abstract:
Steviol glycosides, the active sweet components of stevia plant, have been recently found to possess a number of therapeutic properties, including some recorded anticancer ones against various cancer cell types (breast, ovarian, cervical, pancreatic, and colon cancer). Our aim was to investigate this anticancer potential on the two most commonly used breast cancer cell lines which differ in the phenotype and estrogen receptor (ER) status: the low metastatic, ERα+ MCF-7 and the highly metastatic, ERα-/ERβ+ MDA-MB-231. Specifically, glycosides' effect was studied on cancer cells': (a) viability, (b) functionality (proliferation, migration, and adhesion), and (c) gene expression (mRNA level) of crucial molecules implicated in cancer's pathophysiology. Results showed that steviol glycosides induced cell death in both cell lines, in the first 24 hr, which was in line with the antiapoptotic BCL2 decrease. However, cells that managed to survive showcased diametrically opposite behavior. The low metastatic ERα+ MCF-7 cells acquired an aggressive phenotype, depicted by the upregulation of all receptors and co-receptors (ESR, PGR, AR, GPER1, EGFR, IGF1R, CD44, SDC2, and SDC4), as well as VIM and MMP14. On the contrary, the highly metastatic ERα-/ERβ+ MDA-MB-231 cells became less aggressive as pointed out by the respective downregulation of EGFR, IGF1R, CD44, and SDC2. Changes observed in gene expression were compatible with altered cell functions. Glycosides increased MCF-7 cells migration and adhesion, but reduced MDA-MB-231 cells migratory and metastatic potential. In conclusion, the above data clearly demonstrate that steviol glycosides have different effects on breast cancer cells according to their ER status, suggesting that steviol glycosides might be examined for their potential anticancer activity against breast cancer, especially triple negative breast cancer (TNBC).
Insights
Steviol glycosides from stevia plant show dual effects on breast cancer cells. They induce death in both types but promote aggression in ERα+ cells while reducing it in ERα- cells, suggesting potential for triple-negative breast cancer therapy.
Area of Science:
- Biochemistry and Molecular Biology
- Oncology
- Pharmacology
Background:
- Steviol glycosides, natural sweeteners from the stevia plant, exhibit potential anticancer properties against various cancer types.
- Breast cancer exhibits diverse phenotypes, including estrogen receptor (ER) positive (ERα+) and negative (ERα-) subtypes, influencing treatment response.
- Understanding the differential effects of natural compounds on distinct cancer cell lines is crucial for targeted therapeutic development.
Purpose of the Study:
- To investigate the anticancer effects of steviol glycosides on two distinct human breast cancer cell lines: ERα+ MCF-7 and ERα-/ERβ+ MDA-MB-231.
- To evaluate the impact of steviol glycosides on cancer cell viability, functionality (proliferation, migration, adhesion), and gene expression.
Main Methods:
- Treatment of MCF-7 and MDA-MB-231 cells with steviol glycosides.
- Assessment of cell viability and apoptosis markers (e.g., BCL2 expression).
- Analysis of cell proliferation, migration, and adhesion.
- Gene expression profiling (mRNA level) of key cancer-related molecules (receptors, co-receptors, matrix metalloproteinases).
Main Results:
- Steviol glycosides induced cell death in both cell lines within 24 hours, associated with decreased BCL2 expression.
- ERα+ MCF-7 cells that survived exhibited increased aggressiveness, with upregulated receptors (ESR, PGR, AR, GPER1, EGFR, IGF1R, CD44, SDC2, SDC4) and genes (VIM, MMP14), enhanced migration, and adhesion.
- ERα-/ERβ+ MDA-MB-231 cells that survived showed reduced aggressiveness, with downregulated EGFR, IGF1R, CD44, and SDC2, and decreased migratory and metastatic potential.
Conclusions:
- Steviol glycosides exert differential effects on breast cancer cells contingent upon their ER status.
- The findings suggest a potential role for steviol glycosides in modulating breast cancer cell behavior, particularly in ERα- subtypes.
- Further investigation of steviol glycosides is warranted for their potential therapeutic application, especially against triple-negative breast cancer (TNBC).
