title: The novel mitochondria-targeted antioxidant SkQ1 modulates angiogenesis and inflammatory micromilieu in a murine orthotopic model of pancreatic cancer.
abstract: Our understanding in the last few years about reactive oxygen species (ROS) has changed from being harmful substances to crucial intra- and extracellular messengers as well as important regulators controlling a wide spectrum of signaling pathways, including those in cancer immunology. Therefore, these multiple essential roles of ROS and especially of mitochondria-derived ROS in malignant transformation and cancer progression make them a promising target for anticancer therapy. Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers in the world. A link between ROS, antioxidants and the PDAC development and progression has been recently established. Therefore, usage of specific highly efficient antioxidants could bring an option for treatment and/or prevention of PDAC. 10-(6'-plastoquinonyl) decyltriphenylphosphonium (SkQ1) is a new antioxidant with the highest mitochondrion membrane penetrating ability and potent antioxidant capability. In this work, we investigated an impact of SkQ1 on tumor angiogenesis, immune micromilieu, and oncological parameters in the orthotopic Panc02 murine model of PDAC. We showed that in this model SkQ1 treatment leads to the elevation of pro-angiogenic factors and to building of mainly an anti-inflammatory cytokine milieu. On the cellular level we showed an increase in a percentage of memory T cells and a decrease in frequency on natural killer T (NKT) cells. At the same time, SkQ1 was ineffective in the improvement of oncological parameters of PDAC-bearing mice. New studies are needed to clarify the absence of therapeutic and/or prophylactic benefits of the antioxidant.
authors.affiliation: Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, LMU Munich, Germany.
authors.forename: Alexandr V
authors.initials: AV
authors.lastname: Bazhin
authors.affiliation: Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Yuhui
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, LMU Munich, Germany.
authors.forename: Jan G
authors.initials: JG
authors.lastname: D'Haese
authors.affiliation: Department of General, Visceral, Transplantation, Vascular and Thoracic Surgery, Hospital of the University of Munich, LMU Munich, Germany.
authors.forename: Jens
authors.initials: J
authors.lastname: Werner
authors.affiliation: Department of Cell Signalling, Belozersky Institute of Physico-Chemical Biology, Moscow State University, Moscow, Russia.
authors.forename: Pavel P
authors.initials: PP
authors.lastname: Philippov
authors.affiliation: Department of General Surgery, University Hospital Heidelberg, Germany.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Karakhanova
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage; D021441:Carcinoma, Pancreatic Ductal / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010971:Plastoquinone / Q000008:administration & dosage / Q000031:analogs & derivatives*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C532038:10-(6'-plastoquinonyl)decyltriphenylphosphonium; D000975:Antioxidants; D017382:Reactive Oxygen Species; D010971:Plastoquinone
keywords: PDAC; ROS; SkQ1; angiogenesis; immune regulation