2. Academic Validation
  3. Inhibition of Mitochondrial Antioxidant Defense and CDK4/6 in Mesothelioma

Inhibition of Mitochondrial Antioxidant Defense and CDK4/6 in Mesothelioma

  • Molecules. 2023 May 27;28(11):4380. doi: 10.3390/molecules28114380.
Marian Kratzke 1,  George Scaria 1 2 3,  Stephen Porter 1,  Betsy Kren 1 4,  Mark A Klein 2 3
Affiliations

Affiliations

  • 1 Research Service, Minneapolis VA Health Care System, Minneapolis, MN 55417, USA.
  • 2 Hematology/Oncology Section, Primary Care Service Line, Minneapolis VA Health Care System, Minneapolis, MN 55417, USA.
  • 3 Division of Hematology, Oncology and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN 55417, USA.
  • 4 Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55417, USA.
PMID: 37298855 DOI: 10.3390/molecules28114380
Abstract

Advanced mesothelioma is considered an incurable disease and new treatment strategies are needed. Previous studies have demonstrated that mitochondrial antioxidant defense proteins and the cell cycle may contribute to mesothelioma growth, and that the inhibition of these pathways may be effective against this Cancer. We demonstrated that the antioxidant defense inhibitor auranofin and the cyclin-dependent kinase 4/6 inhibitor palbociclib could decrease mesothelioma cell proliferation alone or in combination. In addition, we determined the effects of these compounds on colony growth, cell cycle progression, and the expression of key antioxidant defense and cell cycle proteins. Auranofin and palbociclib were effective in decreasing cell growth and inhibiting the above-described activity across all assays. Further study of this drug combination will elucidate the contribution of these pathways to mesothelioma activity and may reveal a new treatment strategy.

Keywords

antioxidant; cell cycle; cyclin; cyclin-dependent kinase; mesothelioma; mitochondria.

Figures
Products