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Inhibition of Mitochondrial Redox Signaling with MitoQ Prevents Metastasis of Human Pancreatic Cancer in Mice.

Published version
Peer-reviewed

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Authors

Van de Velde, Justine A 
Lipari, Sara G 
Derouane, Françoise  ORCID logo  https://orcid.org/0000-0002-0199-1366

Abstract

At diagnosis, about 35% of pancreatic cancers are at the locally invasive yet premetastatic stage. Surgical resection is not a treatment option, leaving patients with a largely incurable disease that often evolves to the polymetastatic stage despite chemotherapeutic interventions. In this preclinical study, we hypothesized that pancreatic cancer metastasis can be prevented by inhibiting mitochondrial redox signaling with MitoQ, a mitochondria-targeted antioxidant. Using four different cancer cell lines, we report that, at clinically relevant concentrations (100-500 nM), MitoQ selectively repressed mesenchymal pancreatic cancer cell respiration, which involved the inhibition of the expression of PGC-1α, NRF1 and a reduced expression of electron-transfer-chain complexes I to III. MitoQ consequently decreased the mitochondrial membrane potential and mitochondrial superoxide production by these cells. Phenotypically, MitoQ further inhibited pancreatic cancer cell migration, invasion, clonogenicity and the expression of stem cell markers. It reduced by ~50% the metastatic homing of human MIA PaCa-2 cells in the lungs of mice. We further show that combination treatments with chemotherapy are conceivable. Collectively, this study indicates that the inhibition of mitochondrial redox signaling is a possible therapeutic option to inhibit the metastatic progression of pancreatic cancer.

Description

Peer reviewed: True


Funder: Louvain Foundation


Funder: UCLouvain Fonds Spéciaux de la Recherche (FSR)

Keywords

Article, pancreatic ductal adenocarcinoma (PDAC), cancer metastasis, cancer metabolism, mitochondria, reactive oxygen species (ROS), redox signaling, MitoQ

Journal Title

Cancers (Basel)

Conference Name

Journal ISSN

2072-6694
2072-6694

Volume Title

Publisher

MDPI AG
Sponsorship
European Commission (202213)