Bladder cancer therapy without toxicity—A dose-escalation study of alpha1-oleate
(2020) In International Journal of Cancer 147(9). p.2479-2492- Abstract
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,... (More)
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.
(Less)
- author
- Hien, Tran Thi
LU
; Ambite, Ines
LU
; Butler, Daniel LU ; Wan, Murphy Lam Yim LU ; Tran, Tuan Hiep LU ; Höglund, Urban ; Babjuk, Marek and Svanborg, Catharina LU
- organization
- publishing date
- 2020-11-01
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Alpha1-oleate, bladder cancer therapy, dose escalation, lack of toxicity
- in
- International Journal of Cancer
- volume
- 147
- issue
- 9
- pages
- 14 pages
- publisher
- John Wiley & Sons Inc.
- external identifiers
-
- pmid:32319672
- scopus:85084423337
- ISSN
- 0020-7136
- DOI
- 10.1002/ijc.33019
- language
- English
- LU publication?
- yes
- id
- bc232589-a6eb-404d-80e6-681ffa11aca0
- date added to LUP
- 2020-06-15 11:15:08
- date last changed
- 2024-09-05 22:20:46
@article{bc232589-a6eb-404d-80e6-681ffa11aca0, abstract = {{<p>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.</p>}}, author = {{Hien, Tran Thi and Ambite, Ines and Butler, Daniel and Wan, Murphy Lam Yim and Tran, Tuan Hiep and Höglund, Urban and Babjuk, Marek and Svanborg, Catharina}}, issn = {{0020-7136}}, keywords = {{Alpha1-oleate; bladder cancer therapy; dose escalation; lack of toxicity}}, language = {{eng}}, month = {{11}}, number = {{9}}, pages = {{2479--2492}}, publisher = {{John Wiley & Sons Inc.}}, series = {{International Journal of Cancer}}, title = {{Bladder cancer therapy without toxicity—A dose-escalation study of alpha1-oleate}}, url = {{http://dx.doi.org/10.1002/ijc.33019}}, doi = {{10.1002/ijc.33019}}, volume = {{147}}, year = {{2020}}, }