| MCSWEENEY, K. R., L. K. GADANEC, T. QARADAKHI, T. M. GAMMUNE, P. KUBATKA, M. CAPRNDA, J. FEDOTOVA, J. RADONAK, Peter KRUŽLIAK and A. ZULLI. Imipridone enhances vascular relaxation via FOXO1 pathway. Clinical and Experimental Pharmacology and Physiology. Australia: Blackwell Publishing Australia, 2020, vol. 47, No 11, p. 1816-1823. ISSN 0305-1870. Available from: https://dx.doi.org/10.1111/1440-1681.13377. |
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@article{1680202,
author = {McSweeney, K. R. and Gadanec, L. K. and Qaradakhi, T. and Gammune, T. M. and Kubatka, P. and Caprnda, M. and Fedotova, J. and Radonak, J. and Kružliak, Peter and Zulli, A.},
article_location = {Australia},
article_number = {11},
doi = {http://dx.doi.org/10.1111/1440-1681.13377},
keywords = {acetylcholine; cardiovascular diseases; FOXO1 pathway; imipridone (TIC10); nitric oxide; vascular relaxation},
language = {eng},
issn = {0305-1870},
journal = {Clinical and Experimental Pharmacology and Physiology},
title = {Imipridone enhances vascular relaxation via FOXO1 pathway},
url = {https://onlinelibrary.wiley.com/doi/full/10.1111/1440-1681.13377},
volume = {47},
year = {2020}
}
TY - JOUR
ID - 1680202
AU - McSweeney, K. R. - Gadanec, L. K. - Qaradakhi, T. - Gammune, T. M. - Kubatka, P. - Caprnda, M. - Fedotova, J. - Radonak, J. - Kružliak, Peter - Zulli, A.
PY - 2020
TI - Imipridone enhances vascular relaxation via FOXO1 pathway
JF - Clinical and Experimental Pharmacology and Physiology
VL - 47
IS - 11
SP - 1816-1823
EP - 1816-1823
PB - Blackwell Publishing Australia
SN - 03051870
KW - acetylcholine
KW - cardiovascular diseases
KW - FOXO1 pathway
KW - imipridone (TIC10)
KW - nitric oxide
KW - vascular relaxation
UR - https://onlinelibrary.wiley.com/doi/full/10.1111/1440-1681.13377
L2 - https://onlinelibrary.wiley.com/doi/full/10.1111/1440-1681.13377
N2 - Cardiovascular complications are a side effect of cancer therapy, potentially through reduced blood vessel function. ONC201 (TIC10) is currently used in phase 2 clinical trials to treat high-grade gliomas. TIC10 is a phosphatidylinositol 3-kinase (PI3K)/AKT/extracellular signal-regulated kinase (ERK) inhibitor that induces apoptosis via upregulation of TNF-related apoptosis-inducing ligand, which via stimulation of FOXO and death receptor could increase eNOS upregulation. This has the potential to improve vascular function through increased NO bioavailability. Our aim was to investigate the role of TIC10 on vascular function to determine if it would affect the risk of CVD. Excised abdominal aorta from White New Zealand male rabbits were cut into rings. Vessels were incubated with TIC10 and AS1842856 (FOXO1 inhibitor) followed by cumulative doses of acetylcholine (Ach) to assess vessel function. Vessels were then processed for immunohistochemistry. Incubation of blood vessels with TIC10 resulted in enhanced vasodilatory capacity. Combination treatment with the FOXO1 inhibitor and TIC10 resulted in reduced vascular function compared to control. Immunohistochemical analysis indicated a 3-fold increase in death receptor 5 (DR5) expression in the TIC10-treated blood vessels but the addition of the FOXO1 inhibitor downregulated DR5 expression. The expression of DR4 receptor was not significantly increased in the presence of TIC10; however, addition of the FOXO1 inhibitor downregulated expression. TIC10 has the capacity to improve the function of healthy vessels when stimulated with the vasodilator Ach. This highlights its therapeutic potential not only in cancer treatment without cardiovascular side effects, but also as a possible drug to treat established CVD.
ER -
MCSWEENEY, K. R., L. K. GADANEC, T. QARADAKHI, T. M. GAMMUNE, P. KUBATKA, M. CAPRNDA, J. FEDOTOVA, J. RADONAK, Peter KRUŽLIAK and A. ZULLI. Imipridone enhances vascular relaxation via FOXO1 pathway. \textit{Clinical and Experimental Pharmacology and Physiology}. Australia: Blackwell Publishing Australia, 2020, vol.~47, No~11, p.~1816-1823. ISSN~0305-1870. Available from: https://dx.doi.org/10.1111/1440-1681.13377.
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