PMID- 29212260
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20191120
IS  - 1949-2553 (Electronic)
IS  - 1949-2553 (Linking)
VI  - 8
IP  - 55
DP  - 2017 Nov 7
TI  - Bioenergetics of acquired cisplatin resistant H1299 non-small cell lung cancer 
      and P31 mesothelioma cells.
PG  - 94711-94725
LID - 10.18632/oncotarget.21885 [doi]
AB  - Acquired cisplatin resistance is a common feature of tumours following cancer 
      treatment with cisplatin and also of non-small cell lung cancer (H1299) and 
      mesothelioma (P31) cell lines exposed to cisplatin. To elucidate the cellular 
      basis of acquired cisplatin resistance, a comprehensive bioenergetic analysis was 
      undertaken. We demonstrate that cellular oxygen consumption was significantly 
      decreased in cisplatin resistant cells and that the reduction was primarily due 
      to reduced mitochondrial activity as a result of reduced mitochondrial abundance. 
      The differential mitochondrial abundance was supported by data showing reduced 
      sirtuin 1 (SIRT1), peroxisome-proliferator activator receptor-gamma co-activator 
      1-alpha (PGC1alpha), sirtuin 3 (SIRT3) and mitochondrial transcription factor A 
      (TFAM) protein expression in resistant cells. Consistent with these data we 
      observed increased reactive oxygen species (ROS) production and increased hypoxia 
      inducible factor 1-alpha (HIF1alpha) stabilization in cisplatin resistant cells when 
      compared to cisplatin sensitive controls. We also observed an increase in AMP 
      kinase subunit alpha2 (AMPKalpha2) transcripts and protein expression in resistant H1299 
      cells. mRNA expression was also reduced for cisplatin resistant H1299 cells in 
      these genes, however the pattern was not consistent in resistant P31 cells. There 
      was very little change in DNA methylation of these genes, suggesting that the 
      cells are not stably reprogrammed epigenetically. Taken together, our data 
      demonstrate reduced oxidative metabolism, reduced mitochondrial abundance, 
      potential for increased glycolytic flux and increased ROS production in acquired 
      cisplatin resistant cells. This suggests that the metabolic changes are a result 
      of reduced SIRT3 expression and increased HIF-1alpha stabilization.
FAU - Geoghegan, Fintan
AU  - Geoghegan F
AD  - School of Biochemistry and Immunology, Trinity Biomedical Science Institute 
      (TBSI), Trinity College Dublin, Dublin 2, Ireland.
FAU - Buckland, Robert J
AU  - Buckland RJ
AD  - Dept of Medical Biosciences, Clinical Chemistry, Umea University, Umea, Sweden.
FAU - Rogers, Eric T
AU  - Rogers ET
AD  - School of Biochemistry and Immunology, Trinity Biomedical Science Institute 
      (TBSI), Trinity College Dublin, Dublin 2, Ireland.
FAU - Khalifa, Karima
AU  - Khalifa K
AD  - School of Biochemistry and Immunology, Trinity Biomedical Science Institute 
      (TBSI), Trinity College Dublin, Dublin 2, Ireland.
FAU - O'Connor, Emma B
AU  - O'Connor EB
AD  - School of Biochemistry and Immunology, Trinity Biomedical Science Institute 
      (TBSI), Trinity College Dublin, Dublin 2, Ireland.
FAU - Rooney, Mary F
AU  - Rooney MF
AD  - School of Biochemistry and Immunology, Trinity Biomedical Science Institute 
      (TBSI), Trinity College Dublin, Dublin 2, Ireland.
FAU - Behnam-Motlagh, Parviz
AU  - Behnam-Motlagh P
AD  - Dept of Medical Biosciences, Clinical Chemistry, Umea University, Umea, Sweden.
FAU - Nilsson, Torbjorn K
AU  - Nilsson TK
AD  - Dept of Medical Biosciences, Clinical Chemistry, Umea University, Umea, Sweden.
FAU - Grankvist, Kjell
AU  - Grankvist K
AD  - Dept of Medical Biosciences, Clinical Chemistry, Umea University, Umea, Sweden.
FAU - Porter, Richard K
AU  - Porter RK
AD  - School of Biochemistry and Immunology, Trinity Biomedical Science Institute 
      (TBSI), Trinity College Dublin, Dublin 2, Ireland.
LA  - eng
PT  - Journal Article
DEP - 20171016
PL  - United States
TA  - Oncotarget
JT  - Oncotarget
JID - 101532965
PMC - PMC5706906
OTO - NOTNLM
OT  - SIRT3
OT  - bioenergetics
OT  - cisplatin resistance
OT  - mesothelioma
OT  - non-small cell lung cancer
COIS- CONFLICTS OF INTEREST The authors declared no potential conflicts of interest 
      with respect to the research, authorship, and/or publication of this article.
EDAT- 2017/12/08 06:00
MHDA- 2017/12/08 06:01
PMCR- 2017/11/07
CRDT- 2017/12/08 06:00
PHST- 2017/07/22 00:00 [received]
PHST- 2017/09/21 00:00 [accepted]
PHST- 2017/12/08 06:00 [entrez]
PHST- 2017/12/08 06:00 [pubmed]
PHST- 2017/12/08 06:01 [medline]
PHST- 2017/11/07 00:00 [pmc-release]
AID - 21885 [pii]
AID - 10.18632/oncotarget.21885 [doi]
PST - epublish
SO  - Oncotarget. 2017 Oct 16;8(55):94711-94725. doi: 10.18632/oncotarget.21885. 
      eCollection 2017 Nov 7.