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Anti-Cancer Effects of Cyclic Peptide ALOS4 in a Human Melanoma Mouse Model
- Source :
- International Journal of Molecular Sciences, Volume 22, Issue 17, International Journal of Molecular Sciences, Vol 22, Iss 9579, p 9579 (2021)
- Publication Year :
- 2021
- Publisher :
- Multidisciplinary Digital Publishing Institute, 2021.
-
Abstract
- We examined the effects of ALOS4, a cyclic peptide discovered previously by phage library selection against integrin αvβ3, on a human melanoma (A375) xenograft model to determine its abilities as a potential anti-cancer agent. We found that ALOS4 promoted healthy weight gain in A375-engrafted nude mice and reduced melanoma tumor mass and volume. Despite these positive changes, examination of the tumor tissue did not indicate any significant effects on proliferation, mitotic index, tissue vascularization, or reduction of αSMA or Ki-67 tumor markers. Modulation in overall expression of critical downstream αvβ3 integrin factors, such as FAK and Src, as well as reductions in gene expression of c-Fos and c-Jun transcription factors, indirectly confirmed our suspicions that ALOS4 is likely acting through an integrin-mediated pathway. Further, we found no overt formulation issues with ALOS4 regarding interaction with standard inert laboratory materials (polypropylene, borosilicate glass) or with pH and temperature stability under prolonged storage. Collectively, ALOS4 appears to be safe, chemically stable, and produces anti-cancer effects in a human xenograft model of melanoma. We believe these results suggest a role for ALOS4 in an integrin-mediated pathway in exerting its anti-cancer effects possibly through immune response modulation.
- Subjects :
- Mitotic index
QH301-705.5
integrin
Integrin
Melanoma, Experimental
Mice, Nude
Antineoplastic Agents
Peptides, Cyclic
Article
Catalysis
Inorganic Chemistry
cyclic peptide
Mice
Immune system
Cell Line, Tumor
Gene expression
αvβ3
medicine
melanoma
Animals
Humans
cancer
Physical and Theoretical Chemistry
Biology (General)
Molecular Biology
Transcription factor
QD1-999
Spectroscopy
Mice, Inbred ICR
biology
Chemistry
Melanoma
Organic Chemistry
Cancer
General Medicine
medicine.disease
Xenograft Model Antitumor Assays
Computer Science Applications
biology.protein
Cancer research
ALOS4
Proto-oncogene tyrosine-protein kinase Src
Subjects
Details
- Language :
- English
- ISSN :
- 14220067
- Database :
- OpenAIRE
- Journal :
- International Journal of Molecular Sciences
- Accession number :
- edsair.doi.dedup.....bd295140c1226b73f9da83cd5a0c3c03
- Full Text :
- https://doi.org/10.3390/ijms22179579