Induction of Oxidative Stress and Ferroptosis in Triple-Negative Breast Cancer Cells by Niclosamide via Blockade of the Function and Expression of SLC38A5 and SLC7A11
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View abstract on PubMed
Summary
This summary is machine-generated.The antiparasitic drug niclosamide inhibits amino acid transporters SLC38A5 and SLC7A11 in triple-negative breast cancer (TNBC). This inhibition reduces cancer cell growth and induces ferroptosis, offering a potential therapeutic strategy for TNBC.
Area Of Science
- Biochemistry
- Oncology
- Molecular Biology
Background
- Amino acid transporters SLC38A5 and SLC7A11 are upregulated in triple-negative breast cancer (TNBC).
- SLC38A5 imports amino acids, activating mTOR signaling and epigenetic changes.
- SLC7A11 imports cystine, boosting glutathione and protecting against oxidative stress.
Purpose Of The Study
- Investigate the role of SLC38A5 in selenium-methionine (Se-Met) uptake in TNBC.
- Examine the effects of Se-Met on Nrf2 signaling and SLC7A11 expression.
- Evaluate niclosamide's efficacy in inhibiting SLC38A5 and SLC7A11 and its impact on TNBC progression.
Main Methods
- Assessed SLC38A5 affinity for methionine and Se-Met.
- Analyzed Se-Met's influence on Nrf2 activation and target gene expression.
- Determined niclosamide's inhibitory concentration (IC50) for SLC7A11.
- Measured glutathione levels, cell proliferation, GPX4 expression, and lipid peroxidation.
- Evaluated niclosamide's effect on TNBC xenografts in mice.
Main Results
- SLC38A5 binds methionine and Se-Met with similar affinities.
- Se-Met activates Nrf2, upregulating SLC7A11 expression.
- Niclosamide inhibits SLC7A11 (IC50: 0.1-0.2 μM) and reduces SLC38A5/SLC7A11 expression.
- Niclosamide decreases glutathione, inhibits proliferation, suppresses GPX4, increases lipid peroxidation, and induces ferroptosis.
- Niclosamide significantly reduces MB231 TNBC xenograft growth.
Conclusions
- Niclosamide effectively inhibits SLC38A5 and SLC7A11 in TNBC.
- Niclosamide's inhibition of these transporters leads to ferroptosis and suppressed tumor growth.
- Niclosamide demonstrates therapeutic potential for treating triple-negative breast cancer.
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