Novel Cyclophilin Inhibitor Decreases Cell Proliferation and Tumor Growth in Models of Hepatocellular Carcinoma.

Autor: Simón Serrano S; Translational Cancer Research, Department of Laboratory Medicine, Lund University, Medicon Village, 223 63 Lund, Sweden.; Abliva AB, Medicon Village, Scheelevägen 2, SE-233 81 Lund, Sweden., Tavecchio M; Abliva AB, Medicon Village, Scheelevägen 2, SE-233 81 Lund, Sweden.; Mitochondrial Medicine, Department of Clinical Sciences, Lund University, BMC A13, SE-221 84 Lund, Sweden., Grönberg A; Abliva AB, Medicon Village, Scheelevägen 2, SE-233 81 Lund, Sweden., Sime W; Translational Cancer Research, Department of Laboratory Medicine, Lund University, Medicon Village, 223 63 Lund, Sweden., Jemaà M; Translational Cancer Research, Department of Laboratory Medicine, Lund University, Medicon Village, 223 63 Lund, Sweden., Moss S; Isomerase Therapeutics Ltd., Suite 9, Science Village, Chesterford Research Park, Cambridge CB10 1XL, UK., Gregory MA; Isomerase Therapeutics Ltd., Suite 9, Science Village, Chesterford Research Park, Cambridge CB10 1XL, UK., Gallay P; Department of Immunology & Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA., Elmér E; Abliva AB, Medicon Village, Scheelevägen 2, SE-233 81 Lund, Sweden.; Mitochondrial Medicine, Department of Clinical Sciences, Lund University, BMC A13, SE-221 84 Lund, Sweden., Hansson MJ; Abliva AB, Medicon Village, Scheelevägen 2, SE-233 81 Lund, Sweden.; Mitochondrial Medicine, Department of Clinical Sciences, Lund University, BMC A13, SE-221 84 Lund, Sweden., Massoumi R; Translational Cancer Research, Department of Laboratory Medicine, Lund University, Medicon Village, 223 63 Lund, Sweden.
Jazyk: angličtina
Zdroj: Cancers [Cancers (Basel)] 2021 Jun 18; Vol. 13 (12). Date of Electronic Publication: 2021 Jun 18.
DOI: 10.3390/cancers13123041
Abstrakt: Hepatocellular carcinoma (HCC), the most common primary liver cancer, is usually diagnosed in its late state. Tyrosine kinase inhibitors such as sorafenib and regorafenib are one of the few treatment options approved for advanced HCC and only prolong the patient's life expectancy by a few months. Therefore, there is a need for novel effective treatments. Cyclophilins are intracellular proteins that catalyze the cis/trans isomerization of peptide bonds at proline residues. Cyclophilins are known to be overexpressed in HCC, affecting therapy resistance and cell proliferation. In the present study, we explored the potential of cyclophilin inhibitors as new therapeutic options for HCC in vitro and in vivo. Our results showed that the novel cyclophilin inhibitor, NV651, was able to significantly decrease proliferation in a diverse set of HCC cell lines. The exposure of HCC cells to NV651 caused an accumulation of cells during mitosis and consequent accumulation in the G 2 /M phase of the cell cycle. NV651 reduced tumor growth in vivo using an HCC xenograft model without affecting the body weights of the animals. The safety aspects of NV651 were also confirmed in primary human hepatocytes without any cytotoxic effects. Based on the results obtained in this study, we propose NV651 as a potential treatment strategy for HCC.
Databáze: MEDLINE
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