Restoration of APC gene function in colorectal cancer cells by aminoglycoside- and macrolide-induced read-through of premature termination codons
- 1Department of Anatomy and Anthropology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
- 0Department of Anatomy and Anthropology, Sackler School of Medicine, Tel-Aviv University, Tel-Aviv, Israel.
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View abstract on PubMed
Summary
This summary is machine-generated.Certain antibiotics, like aminoglycosides and macrolides, can restore full-length Adenomatous polyposis coli (APC) protein by read-through of nonsense mutations, offering a potential colorectal cancer therapy.
Area Of Science
- Oncology
- Molecular Biology
- Genetics
Background
- Adenomatous polyposis coli (APC) is a key tumor suppressor protein regulating Wnt signaling.
- Mutations in the APC gene, particularly nonsense mutations, are common in colorectal cancer.
- Restoring functional APC protein is a therapeutic goal for APC-mutated cancers.
Purpose Of The Study
- To investigate the potential of nonsense mutation-read-through-inducing drugs to restore APC function.
- To evaluate the efficacy of aminoglycosides and macrolides in preclinical models of APC-mutated colorectal cancer.
Main Methods
- Utilized reporter plasmids and colorectal cancer cell lines to assess drug-induced read-through of APC nonsense mutations.
- Employed xenograft experiments and the Apc(Min/+) mouse model to evaluate therapeutic effects in vivo.
Main Results
- Several aminoglycosides and tylosin (a macrolide) demonstrated the ability to induce read-through of APC nonsense mutations.
- These compounds significantly ameliorated tumorigenic symptoms in both xenograft and Apc(Min/+) mouse models.
Conclusions
- Nonsense mutation read-through by specific antibiotics is a viable strategy for treating APC-mutated colorectal cancers.
- Aminoglycosides and macrolides show promise as therapeutic agents for restoring APC function and mitigating tumor progression.
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