Chemotherapy with cisplatin: insights into intracellular pH and metabolic landscape of cancer cells in vitro and in vivo

Abstract Although cisplatin plays a central role in cancer chemotherapy, the mechanisms of cell response to this drug have been unexplored. The present study demonstrates the relationships between the intracellular pH (pHi), cell bioenergetics and the response of cervical cancer to cisplatin. pHi wa...

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Autores principales:	Marina V. Shirmanova, Irina N. Druzhkova, Maria M. Lukina, Varvara V. Dudenkova, Nadezhda I. Ignatova, Ludmila B. Snopova, Vladislav I. Shcheslavskiy, Vsevolod V. Belousov, Elena V. Zagaynova
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/1d01ca27978b4309907f9f361f19b0c0
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spelling	oai:doaj.org-article:1d01ca27978b4309907f9f361f19b0c02021-12-02T11:53:06ZChemotherapy with cisplatin: insights into intracellular pH and metabolic landscape of cancer cells in vitro and in vivo10.1038/s41598-017-09426-42045-2322https://doaj.org/article/1d01ca27978b4309907f9f361f19b0c02017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-09426-4https://doaj.org/toc/2045-2322Abstract Although cisplatin plays a central role in cancer chemotherapy, the mechanisms of cell response to this drug have been unexplored. The present study demonstrates the relationships between the intracellular pH (pHi), cell bioenergetics and the response of cervical cancer to cisplatin. pHi was measured using genetically encoded sensor SypHer2 and metabolic state was accessed by fluorescence intensities and lifetimes of endogenous cofactors NAD(P)H and FAD. Our data support the notion that cisplatin induces acidification of the cytoplasm early after the treatment. We revealed in vitro that a capacity of cells to recover and maintain alkaline pHi after the initial acidification is the crucial factor in mediating the cellular decision to survive and proliferate at a vastly reduced rate or to undergo cell death. Additionally, we showed for the first time that pHi acidification occurs after prolonged therapy in vitro and in vivo, and this, likely, favors metabolic reorganization of cells. A metabolic shift from glycolysis towards oxidative metabolism accompanied the cisplatin-induced inhibition of cancer cell growth in vitro and in vivo. Overall, these findings contribute to an understanding of the mechanisms underlying the responsiveness of an individual cell and tumor to therapy and are valuable for developing new therapeutic strategies.Marina V. ShirmanovaIrina N. DruzhkovaMaria M. LukinaVarvara V. DudenkovaNadezhda I. IgnatovaLudmila B. SnopovaVladislav I. ShcheslavskiyVsevolod V. BelousovElena V. ZagaynovaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marina V. Shirmanova Irina N. Druzhkova Maria M. Lukina Varvara V. Dudenkova Nadezhda I. Ignatova Ludmila B. Snopova Vladislav I. Shcheslavskiy Vsevolod V. Belousov Elena V. Zagaynova Chemotherapy with cisplatin: insights into intracellular pH and metabolic landscape of cancer cells in vitro and in vivo
description	Abstract Although cisplatin plays a central role in cancer chemotherapy, the mechanisms of cell response to this drug have been unexplored. The present study demonstrates the relationships between the intracellular pH (pHi), cell bioenergetics and the response of cervical cancer to cisplatin. pHi was measured using genetically encoded sensor SypHer2 and metabolic state was accessed by fluorescence intensities and lifetimes of endogenous cofactors NAD(P)H and FAD. Our data support the notion that cisplatin induces acidification of the cytoplasm early after the treatment. We revealed in vitro that a capacity of cells to recover and maintain alkaline pHi after the initial acidification is the crucial factor in mediating the cellular decision to survive and proliferate at a vastly reduced rate or to undergo cell death. Additionally, we showed for the first time that pHi acidification occurs after prolonged therapy in vitro and in vivo, and this, likely, favors metabolic reorganization of cells. A metabolic shift from glycolysis towards oxidative metabolism accompanied the cisplatin-induced inhibition of cancer cell growth in vitro and in vivo. Overall, these findings contribute to an understanding of the mechanisms underlying the responsiveness of an individual cell and tumor to therapy and are valuable for developing new therapeutic strategies.
format	article
author	Marina V. Shirmanova Irina N. Druzhkova Maria M. Lukina Varvara V. Dudenkova Nadezhda I. Ignatova Ludmila B. Snopova Vladislav I. Shcheslavskiy Vsevolod V. Belousov Elena V. Zagaynova
author_facet	Marina V. Shirmanova Irina N. Druzhkova Maria M. Lukina Varvara V. Dudenkova Nadezhda I. Ignatova Ludmila B. Snopova Vladislav I. Shcheslavskiy Vsevolod V. Belousov Elena V. Zagaynova
author_sort	Marina V. Shirmanova
title	Chemotherapy with cisplatin: insights into intracellular pH and metabolic landscape of cancer cells in vitro and in vivo
title_short	Chemotherapy with cisplatin: insights into intracellular pH and metabolic landscape of cancer cells in vitro and in vivo
title_full	Chemotherapy with cisplatin: insights into intracellular pH and metabolic landscape of cancer cells in vitro and in vivo
title_fullStr	Chemotherapy with cisplatin: insights into intracellular pH and metabolic landscape of cancer cells in vitro and in vivo
title_full_unstemmed	Chemotherapy with cisplatin: insights into intracellular pH and metabolic landscape of cancer cells in vitro and in vivo
title_sort	chemotherapy with cisplatin: insights into intracellular ph and metabolic landscape of cancer cells in vitro and in vivo
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/1d01ca27978b4309907f9f361f19b0c0
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Chemotherapy with cisplatin: insights into intracellular pH and metabolic landscape of cancer cells in vitro and in vivo

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