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Published on: August 8, 2020
[Effects of zearalenone on proliferation and apoptosis in MCF-7 cells]
Zeng-li Yu1, Li-shi Zhang, De-sheng Wu
1School of Public School, Zhengzhou University, Zhengzhou 450052, China.
Objective:
To explore the effects of zearalenone (ZEA) on proliferation and apoptosis in estrogen-dependent human breast cancer MCF-7 cells and the likely underlying molecular mechanisms.
Methods:
Cell viability was determined by MTT assay and cell cycle distribution by cytometry. Apoptosis was detected by Cell Death Detection ELISA and cytometry, respectively. The expressions of bax and bcl-2 were examined using multiple RT-PCR and Western-blot both at mRNA and protein level, respectively.
Results:
The current study confirmed the previous studies that ZEA could stimulate proliferation in MCF-7 cells with inducing a profound increase in S phase and a modest increase in G(2)/M phase that was accompanied by a decrease in G(0)/G(1) phase. ZEA could inhibit apoptosis in MCF-7 cells following estrogen ablation at a range of concentrations of 2 nmol/L -96 nmol/L. Western blot and RT-PCR analysis revealed that the anti-apoptotic bcl-2 was upregulated at both protein and mRNA level, together with the downregulation of pro-apoptotic bax.
Conclusion:
ZEA should have possessed comparative estrogenic activity and could promote the progression of MCF-7 cells through the cell cycle by a decreasing in the G(0)/G(1) phase and by a significant increasing in S-phase. The pro-proliferative activity of ZEA was due to inhibition of apoptosis through regulation of bax/bcl-2 expression.
Insights
Zearalenone (ZEA) promotes human breast cancer MCF-7 cell proliferation by increasing S-phase progression and inhibiting apoptosis. This effect is mediated by upregulating the anti-apoptotic bcl-2 and downregulating the pro-apoptotic bax gene expression.
Area of Science:
- Endocrinology
- Molecular Biology
- Cancer Research
Context:
- Estrogen-dependent breast cancer, like MCF-7 cells, relies on hormonal signaling for growth.
- Zearalenone (ZEA), a mycotoxin, exhibits estrogenic activity, raising concerns about its role in hormone-related cancers.
Purpose:
- To investigate the impact of Zearalenone (ZEA) on the proliferation and apoptosis of estrogen-dependent human breast cancer MCF-7 cells.
- To elucidate the molecular mechanisms underlying ZEA's effects on MCF-7 cell behavior, focusing on cell cycle regulation and apoptosis-related gene expression.
Summary:
- ZEA significantly increased MCF-7 cell proliferation, characterized by a notable shift towards the S phase and a decrease in the G(0)/G(1) phase of the cell cycle.
- ZEA demonstrated anti-apoptotic effects in MCF-7 cells, inhibiting programmed cell death across a range of concentrations (2-96 nmol/L).
- Molecular analysis revealed that ZEA upregulated the anti-apoptotic BCL-2 and downregulated the pro-apoptotic BAX at both mRNA and protein levels, suggesting a mechanism for its anti-apoptotic action.
Impact:
- The findings indicate that ZEA possesses estrogenic activity, potentially promoting breast cancer progression.
- ZEA's ability to inhibit apoptosis via the BAX/BCL-2 pathway highlights its role as a potential endocrine disruptor in breast cancer.
- This research provides crucial insights into the molecular underpinnings of ZEA's carcinogenic potential, informing risk assessment and therapeutic strategies.

