MtDNA depleted PC3 cells exhibit Warburg effect and cancer stem cell features
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Xiaoran Li1,2, Yali Zhong3, Jie Lu4, Karol Axcrona6, Lars Eide5, Randi G. Syljuåsen7, Qian Peng1, Junbai Wang1, Hongquan Zhang8, Mariusz Adam Goscinski9, Gunnar Kvalheim10, Jahn M. Nesland1,2, Zhenhe Suo1,2
1Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, 0379, Norway
2Department of Pathology, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, 0318, Norway
3Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, Henan, 450052, China
4Department of Epidemiology and Biostatistics, College of Public Health, Zhengzhou University, Zhengzhou, Henan, 450001, China
5Department of Medical Biochemistry, University of Oslo and Oslo University Hospital, Oslo, 0372, Norway
6Department of Urology, The Akershus University Hospital, Lørenskog, 1478, Norway
7Department of Radiation Biology, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, 0379, Norway
8Laboratory of Molecular Cell Biology and Tumor Biology, Department of Anatomy, Histology and Embryology, Peking University Health Science Center, Beijing, 100191, China
9Department of Surgery, The Norwegian Radium Hospital, Oslo University Hospital, Institute for Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, 0379, Norway
10Department of Cell Therapy, Cancer Institute, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, 0379, Norway
Zhenhe Suo, email: email@example.com
Keywords: mitochondrial DNA, Warburg effect, hypoxia, transcriptome analysis, cancer stem cells
Received: February 22, 2016 Accepted: April 29, 2016 Published: May 26, 2016
Reducing mtDNA content was considered as a critical step in the metabolism restructuring for cell stemness restoration and further neoplastic development. However, the connections between mtDNA depletion and metabolism reprograming-based cancer cell stemness in prostate cancers are still lack of studies. Here, we demonstrated that human CRPC cell line PC3 tolerated high concentration of the mtDNA replication inhibitor ethidium bromide (EtBr) and the mtDNA depletion triggered a universal metabolic remodeling process. Failure in completing that process caused lethal consequences. The mtDNA depleted (MtDP) PC3 cells could be steadily maintained in the special medium in slow cycling status. The MtDP PC3 cells contained immature mitochondria and exhibited Warburg effect. Furthermore, the MtDP PC3 cells were resistant to therapeutic treatments and contained greater cancer stem cell-like subpopulations: CD44+, ABCG2+, side-population and ALDHbright. In conclusion, these results highlight the association of mtDNA content, mitochondrial function and cancer cell stemness features.
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