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Published on: April 25, 2025
BH3-based fusion artificial peptide induces apoptosis and targets human colon cancer
Yongjun Liu1, Yunfeng Li, Haijuan Wang
1State Key Laboratory of Molecular Oncology, Cancer Institute, Chinese Academy of Medical Sciences, Beijing, China.
Abstract:
Dysregulation of apoptosis is a pilot event before cancer development and plays important roles for cancer to develop resistance to chemical therapeutics. So exploring strategies to recovery the apoptosis balance is a charming and long-endeavored aim in the attempts to conquer cancers. The present study shows an exciting potency of a fusion peptide to inhibit and target to cancer cells, which is composed of BH3 (Bcl-2 Homology 3) effector domain from PUMA (p53 upregulated modulator of apoptosis) and targeting domain of trans-activator of transcription (TAT) and DV3. The in vitro results demonstrated cancer growth inhibition by the fusion peptide in colon cancer cells, as well as in lung adenocarcinoma cell line and breast carcinoma cell line of human origin. But the viability of HEK293, a noncancerous cell line, was not affected, indicating the cancer specificity of the fusion peptide. Apoptosis activation was induced by the peptide through the mitochondria pathway. In vivo studies displayed its tumor inhibiting ability by intratumoral injection. When the fusion peptide was administered systematically by tail vein, the peptide targeted the established tumors in nude mice. No other organs were significantly involved. The fusion peptide is an artificially designed molecule worthy of further evaluation and development.
Insights
A novel fusion peptide effectively inhibits cancer cell growth and targets tumors, activating apoptosis via the mitochondria pathway. This cancer-specific molecule shows promise for further development in oncology treatments.
Area of Science:
- Oncology
- Molecular Biology
- Biotechnology
Background:
- Dysregulation of apoptosis is a key factor in cancer development and therapeutic resistance.
- Restoring apoptosis balance is a critical goal in cancer therapy.
Purpose of the Study:
- To evaluate the potential of a novel fusion peptide for cancer treatment.
- To assess the peptide's ability to inhibit cancer cell growth and target tumors specifically.
Main Methods:
- In vitro studies using colon, lung, and breast cancer cell lines, along with HEK293 noncancerous cells.
- In vivo studies involving intratumoral injection and systemic administration (tail vein) in nude mice.
- Analysis of apoptosis activation through the mitochondria pathway.
Main Results:
- The fusion peptide demonstrated significant cancer cell growth inhibition in vitro.
- The peptide exhibited cancer specificity, sparing noncancerous HEK293 cells.
- In vivo studies confirmed tumor inhibition and targeted delivery to established tumors without affecting other organs.
- Apoptosis was induced via the mitochondria pathway.
Conclusions:
- The designed fusion peptide, comprising PUMA's BH3 effector domain and TAT/DV3 targeting domains, shows potent anti-cancer activity.
- The peptide is cancer-specific and effectively inhibits tumor growth in vivo.
- This fusion peptide represents a promising candidate for further preclinical evaluation and therapeutic development.
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