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Published on: June 30, 2023
The pro-apoptotic role of autophagy in breast cancer
11] Department of Biomedical Sciences, Paul L Foster school of Medicine, Texas Tech University Health Sciences center, El Paso, TX, USA [2] Department of Urology, University of Louisville, KY 40202, USA.
Background:
Autophagy is a catabolic process that has a vital role in cancer progression and treatment. Current chemotherapeutic agents, which target autophagy, result in growth inhibition in many cancer types. In this study, we examined the role of autophagy in breast cancer (BCa) patients as well as BCa cell lines.
Methods:
Tissue microarray was used to detect the expression of an autophagy marker, LC3B in BCa patients (normal/hyperplasia=8; grade-I=15, grade-II=84, and grade-III=27) and BCa cell lines. To modulate the activation of autophagy, we used novel herbal compound nimocinol acetate (NA) in BCa cell lines and the anticancer activity was measured by phenotypic and molecular analysis.
Results:
LC3B is highly expressed in tumours as compared with normal tissues. Activation of LC3B in NA-treated BCa (MCF-7 and MDA-MB-231) cells was evident as compared with other autophagy makers. Further, our results confirmed that NA-transcriptionally regulates LC3B (as confirmed by mRNA levels and reporter assay), which resulted in the formation of acidic autophagy vesicles and autolysosomes in BCa cells. Nimocinol acetate inhibited mTOR-mediated pro-survival signalling that resulted in inhibition of growth in BCa cells without affecting normal breast epithelial cells. Downregulation of LC3B expression by siRNA significantly inhibited the anticancer effects of NA in BCa cells.
Conclusions:
Together, our results suggest that LC3B is highly expressed in BCa tissues and increasing the threshold of LC3B activation dictates the pro-apoptotic function, which in turn, suppresses the growth of BCa cells. Nimocinol acetate could be a potential agent for treatment of BCa.
Insights
Autophagy marker LC3B is highly expressed in breast cancer (BCa). The herbal compound nimocinol acetate (NA) activates LC3B, suppressing BCa cell growth and showing potential as a BCa treatment.
Area of Science:
- Oncology
- Cell Biology
- Pharmacology
Background:
- Autophagy plays a critical role in cancer progression and treatment response.
- Targeting autophagy with chemotherapeutic agents can inhibit cancer growth.
- This study investigates autophagy's role in breast cancer (BCa).
Purpose of the Study:
- To examine the expression of autophagy marker LC3B in BCa patients and cell lines.
- To evaluate the effect of nimocinol acetate (NA) on autophagy activation and BCa cell growth.
Main Methods:
- Tissue microarray analysis of LC3B expression in BCa tissues.
- Treatment of BCa cell lines with nimocinol acetate (NA) to modulate autophagy.
- Phenotypic and molecular analyses to assess anticancer activity.
Main Results:
- LC3B expression is significantly higher in BCa tumors compared to normal tissues.
- NA treatment upregulated LC3B, leading to increased autophagy vesicles and autolysosomes in BCa cells.
- NA inhibited mTOR signaling, suppressed BCa cell growth without affecting normal cells, and its effects were dependent on LC3B.
Conclusions:
- Elevated LC3B expression in BCa tissues suggests its role in cancer progression.
- Increased LC3B activation by NA promotes apoptosis and suppresses BCa cell growth.
- Nimocinol acetate demonstrates potential as a therapeutic agent for breast cancer.
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