Application of mitochondrial pyruvate carrier blocker UK5099 creates metabolic reprogram and greater stem-like properties in LnCap prostate cancer cells in vitro
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Yali Zhong1,2,3,4, Xiaoran Li3,4, Dandan Yu1, Xiaoli Li1, Yaqing Li1, Yuan Long5, Yuan Yuan6, Zhenyu Ji7, Mingzhi Zhang1, Jian-Guo Wen8, Jahn M. Nesland3,4, Zhenhe Suo1,3,4
1Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
2Department of Gastroenterology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
3Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, University of Oslo, Montebello, Oslo, Norway
4Department of Pathology, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
5Department of Surgery, The Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, Henan Province, China
6Department of Pathology, Capital Medical University, Beijing, China
7Department of Oncology, Henan Academy of Medical and Pharmaceutical Sciences, Zhengzhou University, Zhengzhou, Henan Province, China
8Department of Urology Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Henan, China
Zhenhe Suo, e-mail: [email protected]
Keywords: MPC blocker, mitochondrial dysfunction, glycolysis, stemness
Received: July 09, 2015 Accepted: September 14, 2015 Published: September 25, 2015
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.
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