Multiparametric analysis of cisplatin-induced changes in cancer cells using FLIM

Marina V. Shirmanova, Tatiana F. Sergeeva, Alena I. Gavrina, Varvara V. Dudenkova, Konstantin A. Lukyanov, Elena V. Zagaynova

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

Abstract

Cisplatin is an effective anticancer drug commonly used in the treatment of solid tumors. Although DNA is considered as the primary target, the cisplatin action at the cellular level remains unknown. Advanced fluorescence microscopy techniques allow probing various physiological and physicochemical parameters in living cells and tissues with unsurpassed sensitivity in real time. This study was focused on the investigation of cellular bioenergetics and cytosolic pH in colorectal cancer cells during chemotherapy with cisplatin. Special attention was given to the changes in cisplatininduced apoptosis that was identified using genetically encoded FLIM/FRET sensor of caspase-3 activity. Metabolic measurements using FLIM of the metabolic cofactor NAD(P)H showed decreased contribution from free NAD(P)H (a1, %) in all treated cells with more pronounced alterations in the cells undergoing apoptosis. Analysis of cytosolic pH using genetically encoded fluorescent sensor SypHer1 revealed a rapid increase of the pH value upon cisplatin exposure irrespective of the induction of apoptosis. To the best of our knowledge, a simultaneous assessment of metabolic state, cytosolic pH and caspase-3 activity after treatment with cisplatin was performed for the first time. These findings improve our understanding of the cell response to chemotherapy and mechanisms of cisplatin action.

Original languageEnglish
Title of host publicationMultiphoton Microscopy in the Biomedical Sciences XVIII
EditorsAmmasi Periasamy, Xiaoliang S. Xie, Xiaoliang S. Xie, Karsten Konig, Peter T. C. So
PublisherSPIE
ISBN (Electronic)9781510614819
DOIs
Publication statusPublished - 2018
Externally publishedYes
EventMultiphoton Microscopy in the Biomedical Sciences XVIII 2018 - San Francisco, United States
Duration: 28 Jan 201830 Jan 2018

Publication series

NameProgress in Biomedical Optics and Imaging - Proceedings of SPIE
Volume10498
ISSN (Print)1605-7422

Conference

ConferenceMultiphoton Microscopy in the Biomedical Sciences XVIII 2018
Country/TerritoryUnited States
CitySan Francisco
Period28/01/1830/01/18

Keywords

  • apoptosis
  • cisplatin
  • colorectal cancer cells
  • cytosolic pH
  • genetically encoded sensors
  • metabolic status

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