Publication detail

Drug Sequestration in Lysosomes as One of the Mechanisms of Chemoresistance of Cancer Cells and the Possibilities of Its Inhibition

HRABĚTA, J. BELHAJOVÁ, M. ŠUBRTOVÁ, H. MERLOS RODRIGO, M. HEGER, Z. ECKSCHLAGER, T.

Original Title

Drug Sequestration in Lysosomes as One of the Mechanisms of Chemoresistance of Cancer Cells and the Possibilities of Its Inhibition

Type

journal article in Web of Science

Language

English

Original Abstract

Resistance to chemotherapeutics and targeted drugs is one of the main problems in successful cancer therapy. Various mechanisms have been identified to contribute to drug resistance. One of those mechanisms is lysosome-mediated drug resistance. Lysosomes have been shown to trap certain hydrophobic weak base chemotherapeutics, as well as some tyrosine kinase inhibitors, thereby being sequestered away from their intracellular target site. Lysosomal sequestration is in most cases followed by the release of their content from the cell by exocytosis. Lysosomal accumulation of anticancer drugs is caused mainly by ion-trapping, but active transport of certain drugs into lysosomes was also described. Lysosomal low pH, which is necessary for ion-trapping is achieved by the activity of the V-ATPase. This sequestration can be successfully inhibited by lysosomotropic agents and V-ATPase inhibitors in experimental conditions. Clinical trials have been performed only with lysosomotropic drug chloroquine and their results were less successful. The aim of this review is to give an overview of lysosomal sequestration and expression of acidifying enzymes as yet not well known mechanism of cancer cell chemoresistance and about possibilities how to overcome this form of resistance.

Keywords

chemoresistance of cancer cells; lysosomal sequestration; V-ATPase; metallothioneins; lysosomotropic agents; V-ATPase inhibitors

Authors

HRABĚTA, J.; BELHAJOVÁ, M.; ŠUBRTOVÁ, H.; MERLOS RODRIGO, M.; HEGER, Z.; ECKSCHLAGER, T.

Released

30. 6. 2020

Publisher

MDPI

ISBN

1422-0067

Periodical

International Journal of Molecular Sciences

Year of study

21

Number

12

State

Swiss Confederation

Pages from

1

Pages to

18

Pages count

18

URL

https://www.mdpi.com/1422-0067/21/12/4392

Full text in the Digital Library

http://hdl.handle.net/11012/194873

BibTex

@article{BUT164789,
  author="Jan {Hraběta} and Marie {Belhajová} and Hana {Šubrtová} and Miguel Ángel {Merlos Rodrigo} and Zbyněk {Heger} and Tomáš {Eckschlager}",
  title="Drug Sequestration in Lysosomes as One of the Mechanisms of Chemoresistance of Cancer Cells and the Possibilities of Its Inhibition",
  journal="International Journal of Molecular Sciences",
  year="2020",
  volume="21",
  number="12",
  pages="1--18",
  doi="10.3390/ijms21124392",
  issn="1422-0067",
  url="https://www.mdpi.com/1422-0067/21/12/4392"
}