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Sökning: WFRF:(Buckland Robert J) > (2015-2019) > Bioenergetics of ac...

  • Geoghegan, Fintan (författare)

Bioenergetics of acquired cisplatin resistant H1299 non-small cell lung cancer and P31 mesothelioma cells

  • Artikel/kapitelEngelska2017

Förlag, utgivningsår, omfång ...

  • 2017-10-16
  • IMPACT JOURNALS LLC,2017
  • printrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:umu-142242
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-142242URI
  • https://doi.org/10.18632/oncotarget.21885DOI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • 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 (PGC1 alpha), 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 (HIF1 alpha) stabilization in cisplatin resistant cells when compared to cisplatin sensitive controls. We also observed an increase in AMP kinase subunit alpha 2 (AMPK alpha 2) 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-1 alpha stabilization.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Buckland, Robert J.Umeå universitet,Klinisk kemi(Swepub:umu)robu0005 (författare)
  • Rogers, Eric T. (författare)
  • Khalifa, Karima (författare)
  • O'Connor, Emma B. (författare)
  • Rooney, Mary F. (författare)
  • Behnam-Motlagh, ParvizUmeå universitet,Klinisk kemi(Swepub:umu)pabe0001 (författare)
  • Nilsson, Torbjörn K.Umeå universitet,Klinisk kemi(Swepub:umu)toni0049 (författare)
  • Grankvist, KjellUmeå universitet,Klinisk kemi(Swepub:umu)kjgr0002 (författare)
  • Porter, Richard K. (författare)
  • Umeå universitetKlinisk kemi (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Oncotarget: IMPACT JOURNALS LLC8:55, s. 94711-947251949-2553

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