Bladder cancer therapy without toxicity—A dose-escalation study of alpha1-oleate

Tran Thi Hien, Ines Ambite, Daniel Butler, Murphy Lam Yim Wan, Tuan Hiep Tran, Urban Höglund, Marek Babjuk, Catharina Svanborg

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskriftPeer review

4 Citeringar (SciVal)

Sammanfattning

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.

Originalspråkengelska
Sidor (från-till)2479-2492
Antal sidor14
TidskriftInternational Journal of Cancer
Volym147
Utgåva9
Tidigt onlinedatum2020 apr 22
DOI
StatusPublished - 2020 nov 1

Ämnesklassifikation (UKÄ)

  • Cancer och onkologi
  • Cell- och molekylärbiologi

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