Bladder cancer therapy without toxicity-A dose-escalation study of alpha1-oleate
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
32319672
DOI
10.1002/ijc.33019
Knihovny.cz E-resources
- Keywords
- Alpha1-oleate, bladder cancer therapy, dose escalation, lack of toxicity,
- MeSH
- Administration, Intravesical MeSH
- Rabbits MeSH
- Oleic Acid administration & dosage chemistry toxicity MeSH
- Lactalbumin administration & dosage chemistry toxicity MeSH
- Humans MeSH
- Urinary Bladder drug effects pathology MeSH
- Disease Models, Animal MeSH
- Mice MeSH
- Cell Line, Tumor transplantation MeSH
- Urinary Bladder Neoplasms drug therapy pathology MeSH
- Antineoplastic Agents administration & dosage chemistry toxicity MeSH
- Drug Screening Assays, Antitumor MeSH
- Toxicity Tests, Subchronic MeSH
- Animals MeSH
- Check Tag
- Rabbits MeSH
- Humans MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Oleic Acid MeSH
- Lactalbumin MeSH
- Antineoplastic Agents MeSH
Potent chemotherapeutic agents are required to counteract the aggressive behavior of cancer cells and patients often experience severe side effects, due to tissue toxicity. Our study addresses if a better balance between efficacy and toxicity can be attained using the tumoricidal complex alpha1-oleate, formed by a synthetic, alpha-helical peptide comprising the N-terminal 39 amino acids of alpha-lactalbumin and the fatty acid oleic acid. Bladder cancer was established, by intravesical instillation of MB49 cells on day 0 and the treatment group received five instillations of alpha1-oleate (1.7-17 mM) on days 3 to 11. A dose-dependent reduction in tumor size, bladder size and bladder weight was recorded in the alpha1-oleate treated group, compared to sham-treated mice. Tumor markers Ki-67, Cyclin D1 and VEGF were inhibited in a dose-dependent manner, as was the expression of cancer-related genes. Remarkably, toxicity for healthy tissue was not detected in alpha1-oleate-treated, tumor-bearing mice or healthy mice or rabbits, challenged with increasing doses of the active complex. The results define a dose-dependent therapeutic effect of alpha1-oleate in a murine bladder cancer model.
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