title: Application of mitochondrial pyruvate carrier blocker UK5099 creates metabolic reprogram and greater stem-like properties in LnCap prostate cancer cells in vitro.
abstract: Aerobic glycolysis is one of the important hallmarks of cancer cells and eukaryotic cells. In this study, we have investigated the relationship between blocking mitochondrial pyruvate carrier (MPC) with UK5099 and the metabolic alteration as well as stemness phenotype of prostatic cancer cells. It was found that blocking pyruvate transportation into mitochondrial attenuated mitochondrial oxidative phosphorylation (OXPHOS) and increased glycolysis. The UK5099 treated cells showed significantly higher proportion of side population (SP) fraction and expressed higher levels of stemness markers Oct3/4 and Nanog. Chemosensitivity examinations revealed that the UK5099 treated cells became more resistant to chemotherapy compared to the non-treated cells. These results demonstrate probably an intimate connection between metabolic reprogram and stem-like phenotype of LnCap cells in vitro. We propose that MPC blocker (UK5099) application may be an ideal model for Warburg effect studies, since it attenuates mitochondrial OXPHOS and increases aerobic glycolysis, a phenomenon typically reflected in the Warburg effect. We conclude that impaired mitochondrial OXPHOS and upregulated glycolysis are related with stem-like phenotype shift in prostatic cancer cells.
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.|Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.|Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, University of Oslo, Montebello, Oslo, Norway.|Department of Pathology, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Yali
authors.initials: Y
authors.lastname: Zhong
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, University of Oslo, Montebello, Oslo, Norway.|Department of Pathology, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Xiaoran
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Yu
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
authors.forename: Yaqing
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Long
authors.affiliation: Department of Pathology, Capital Medical University, Beijing, China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Department of Oncology, Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province, China.
authors.forename: Zhenyu
authors.initials: Z
authors.lastname: Ji
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
authors.forename: Mingzhi
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Urology Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan, China.
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Wen
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, University of Oslo, Montebello, Oslo, Norway.|Department of Pathology, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Jahn M
authors.initials: JM
authors.lastname: Nesland
authors.affiliation: Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.|Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, University of Oslo, Montebello, Oslo, Norway.|Department of Pathology, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
authors.forename: Zhenhe
authors.initials: Z
authors.lastname: Suo
mesh_terms: D000179:Acrylates / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D005434:Flow Cytometry; D006019:Glycolysis / Q000187:drug effects; D006801:Humans; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D026901:Membrane Transport Proteins / Q000737:chemistry*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D033681:Mitochondrial Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; D014411:Neoplastic Stem Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010085:Oxidative Phosphorylation / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000179:Acrylates; D000970:Antineoplastic Agents; C573718:MPC1 protein, human; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D027501:Monocarboxylic Acid Transporters; D017382:Reactive Oxygen Species; C043654:2-cyano-3-(1-phenylindol-3-yl)acrylate
keywords: MPC blocker; glycolysis; mitochondrial dysfunction; stemness