Zosuquidar: An Effective Molecule for Intracellular Ca2+ Measurement in P-gp Positive Cells

Pelegrinova, Livia; Sofrankova, Lucia; Spaldova, Jana; Stefik, Pavol; Sulova, Zdena; Breier, Albert; Elefantova, Katarina

doi:10.3390/ijms25063107

Open AccessArticle

Zosuquidar: An Effective Molecule for Intracellular Ca²⁺ Measurement in P-gp Positive Cells

by

Livia Pelegrinova

^1,2,†

,

Lucia Sofrankova

^2,†

,

Jana Spaldova

²,

Pavol Stefik

²,

Zdena Sulova

¹

,

Albert Breier

^1,2,*

and

Katarina Elefantova

^2,‡

¹

Institute of Molecular Physiology and Genetics, Centre of Bioscience, Slovak Academy of Sciences, Dúbravská Cesta 9, 845 05 Bratislava, Slovakia

²

Institute of Biochemistry and Microbiology, Faculty of Chemical and Food Technology, Slovak University of Technology in Bratislava, Radlinského 9, 812 37 Bratislava, Slovakia

^*

Author to whom correspondence should be addressed.

^†

These authors contributed equally to this work.

^‡

Our colleague suddenly passed away in 2023.

Int. J. Mol. Sci. 2024, 25(6), 3107; https://doi.org/10.3390/ijms25063107

Submission received: 24 January 2024 / Revised: 1 March 2024 / Accepted: 5 March 2024 / Published: 7 March 2024

(This article belongs to the Section Biochemistry)

Download

Browse Figures

Review Reports Versions Notes

Abstract

Intracellular calcium, as a second messenger, is involved in multilevel cellular regulatory pathways and plays a role (among other processes) in switching between survival and initiation of cell death in neoplastic cells. The development of multidrug resistance (MDR) in neoplastic cells is associated with the ability of cells to escape programmed cell death, in which dysregulation of intracellular calcium may play an important role. Therefore, reliable monitoring of intracellular calcium levels is necessary. However, such a role might be limited by a real obstacle since several fluorescent intracellular calcium indicators are substrates of membrane ABC drug transporters. For example, Fluo-3/AM is a substrate of P-glycoprotein (ABCB1 member of the ABC family), whose overexpression is the most frequent cause of MDR. The overexpression of ABCB1 prevents MDR cell variants from retaining this tracer in the intracellular space where it is supposed to detect calcium. The solution is to use a proper inhibitor of P-gp efflux activity to ensure the retention of the tracer inside the cells. The present study showed that Zosuquidar and Tariquidar (P-gp inhibitors) are suitable for monitoring intracellular calcium, either by flow cytometry or confocal microscopy, in cells overexpressing P-gp.

Keywords: Zosuquidar; Fluo-3/AM; flow cytometry; P-glycoprotein; multidrug resistance

Graphical Abstract

Share and Cite

MDPI and ACS Style

Pelegrinova, L.; Sofrankova, L.; Spaldova, J.; Stefik, P.; Sulova, Z.; Breier, A.; Elefantova, K. Zosuquidar: An Effective Molecule for Intracellular Ca²⁺ Measurement in P-gp Positive Cells. Int. J. Mol. Sci. 2024, 25, 3107. https://doi.org/10.3390/ijms25063107

AMA Style

Pelegrinova L, Sofrankova L, Spaldova J, Stefik P, Sulova Z, Breier A, Elefantova K. Zosuquidar: An Effective Molecule for Intracellular Ca²⁺ Measurement in P-gp Positive Cells. International Journal of Molecular Sciences. 2024; 25(6):3107. https://doi.org/10.3390/ijms25063107

Chicago/Turabian Style

Pelegrinova, Livia, Lucia Sofrankova, Jana Spaldova, Pavol Stefik, Zdena Sulova, Albert Breier, and Katarina Elefantova. 2024. "Zosuquidar: An Effective Molecule for Intracellular Ca²⁺ Measurement in P-gp Positive Cells" International Journal of Molecular Sciences 25, no. 6: 3107. https://doi.org/10.3390/ijms25063107

APA Style

Pelegrinova, L., Sofrankova, L., Spaldova, J., Stefik, P., Sulova, Z., Breier, A., & Elefantova, K. (2024). Zosuquidar: An Effective Molecule for Intracellular Ca²⁺ Measurement in P-gp Positive Cells. International Journal of Molecular Sciences, 25(6), 3107. https://doi.org/10.3390/ijms25063107

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Menu

Zosuquidar: An Effective Molecule for Intracellular Ca²⁺ Measurement in P-gp Positive Cells

Abstract

Share and Cite

Article Metrics

Article Access Statistics

Further Information

Guidelines

MDPI Initiatives

Follow MDPI