Lysosomal sequestration of weak base drugs, lysosomal biogenesis, and cell cycle alteration
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15110%2F22%3A73615586" target="_blank" >RIV/61989592:15110/22:73615586 - isvavai.cz</a>
Result on the web
<a href="https://www.sciencedirect.com/science/article/pii/S075333222200717X?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S075333222200717X?via%3Dihub</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1016/j.biopha.2022.113328" target="_blank" >10.1016/j.biopha.2022.113328</a>
Alternative languages
Result language
angličtina
Original language name
Lysosomal sequestration of weak base drugs, lysosomal biogenesis, and cell cycle alteration
Original language description
Lysosomes, now known to take part in multiple cellular functions, also respond to various stress stimuli. These include biogenesis in response to nanomolar concentrations of hydrophobic weak-base anticancer drugs. However, since lysosomal stress mediated by accumulation of weak-base drugs at such concentrations has never been proven and these drugs have diverse effects on malignant cells, we investigated whether the interpretation of the data was true. We found that lysosomal accumulation of the drugs daunorubicin, doxorubicin, mitoxantrone, symadex, chloroquine, clomipramine and sunitinib alone, was insufficient to induce lysosomal alkalization i.e., lysosomal stress-mediated biogenesis at nanomolar concentrations. Instead, we found that some of the drugs used induced G2 phase arrest and lysosomal biogenesis that is associated with activation of transcription factor EB (TFEB). Similarly, cantharidin, a control compound that does not belong to the weak base drugs, induced cell cycle arrest in the G2 phase associated with TFEB-driven lysosomal biogenesis. Overall none of the tested drugs caused stress-induced lysosomal biogenesis at nanomolar concentrations. However, daunorubicin, doxorubicin, mitoxantrone, symadex and cantharidin induced a massive block in the G2 phase of the cell cycle which is naturally associated with TFEB-driven lysosomal biogenesis.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
10608 - Biochemistry and molecular biology
Result continuities
Project
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Continuities
S - Specificky vyzkum na vysokych skolach
Others
Publication year
2022
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
BIOMEDICINE & PHARMACOTHERAPY
ISSN
0753-3322
e-ISSN
1950-6007
Volume of the periodical
153
Issue of the periodical within the volume
září 2022
Country of publishing house
FR - FRANCE
Number of pages
22
Pages from-to
113328
UT code for WoS article
000827236200004
EID of the result in the Scopus database
2-s2.0-85133451487