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Oncotarget. 2015 Nov 10;6(35):37758-69. doi: 10.18632/oncotarget.5386.

Application of mitochondrial pyruvate carrier blocker UK5099 creates metabolic reprogram and greater stem-like properties in LnCap prostate cancer cells in vitro.

Zhong Y1,2,3,4, Li X3,4, Yu D1, Li X1, Li Y1, Long Y5, Yuan Y6, Ji Z7, Zhang M1, Wen JG8, Nesland JM3,4, Suo Z1,3,4.

Author information

1
Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
2
Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
3
Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, University of Oslo, Montebello, Oslo, Norway.
4
Department of Pathology, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
5
Department of Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
6
Department of Pathology, Capital Medical University, Beijing, China.
7
Department of Oncology, Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province, China.
8
Department of Urology Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan, China.

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.

KEYWORDS:

MPC blocker; glycolysis; mitochondrial dysfunction; stemness

PMID:
26413751
PMCID:
PMC4741963
DOI:
10.18632/oncotarget.5386
[Indexed for MEDLINE]
Free PMC Article

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