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Journal articles
Triarylpyridine Compounds and Chloroquine Act in Concert to Trigger Lysosomal Membrane Permeabilization and Cell Death in Cancer Cells
Abstract : Lysosomes play a key role in regulating cell death in response to cancer therapies, yet little is known on the possible role of lysosomes in the therapeutic efficacy of G-quadruplex DNA ligands (G4L) in cancer cells. Here, we investigate the relationship between the modulation of lysosomal membrane damage and the degree to which cancer cells respond to the cytotoxic effects of G-quadruplex ligands belonging to the triarylpyridine family. Our results reveal that the lead compound of this family, 20A promotes the enlargement of the lysosome compartment as well as the induction of lysosome-relevant mRNAs. Interestingly, the combination of 20A and chloroquine (an inhibitor of lysosomal functions) led to a significant induction of lysosomal membrane permeabilization coupled to massive cell death. Similar effects were observed when chloroquine was added to three new triarylpyridine derivatives. Our findings thus uncover the lysosomal effects of triarylpyridines compounds and delineate a rationale for combining these compounds with chloroquine to increase their anticancer effects.
Cited literature [63 references]
https://www.hal.inserm.fr/inserm-02951199
Contributor : Jean-Louis Mergny <>
Submitted on : Monday, September 28, 2020 - 3:30:07 PM
Last modification on : Monday, December 14, 2020 - 9:53:06 AM
Long-term archiving on: : Tuesday, December 29, 2020 - 6:41:42 PM
Contributor : Jean-Louis Mergny <>
Submitted on : Monday, September 28, 2020 - 3:30:07 PM
Last modification on : Monday, December 14, 2020 - 9:53:06 AM
Long-term archiving on: : Tuesday, December 29, 2020 - 6:41:42 PM
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2020 Cancers Beauvarlet (Lysos...
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