Cytosolic JNK-dependent microtubule reassembly protects Jurkat leukemia cells from selenite-induced apoptosis.
Apoptosis
JNK
Microtubule
Re-assembly
Selenite
Journal
Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS)
ISSN: 1878-3252
Titre abrégé: J Trace Elem Med Biol
Pays: Germany
ID NLM: 9508274
Informations de publication
Date de publication:
Sep 2023
Sep 2023
Historique:
received:
03
06
2022
revised:
12
05
2023
accepted:
17
05
2023
medline:
7
8
2023
pubmed:
25
5
2023
entrez:
24
5
2023
Statut:
ppublish
Résumé
Selenite at high dosage exhibits great potential in curing tumors. It has been shown that selenite inhibits tumor growth through regulation of microtubule dynamics, however, the exact underlying mechanisms remained to be fully elucidated. Western blots were carried out to evaluate expression level of different molecules. Our current study discovered that selenite induced microtubule disassembly, cell cycle arrest and finally resulted in apoptosis in Jurkat leukemia cells, while during this process disassembled tubulins were re-organized after long-term exposure to selenite. Furthermore, JNK was activated in the cytoplasm of selenite-treated Jurkat cells, and inhibition of JNK activity successfully prevented the process of microtubule re-assembly. Moreover, inactivation of JNK further enhanced selenite-induced cell cycle arrest and apoptosis. According to the results from cell counting-8 assay, blockage of microtubule re-assembly by colchicine further inhibited Jurkat cell viability after exposure to selenite. Experiments in a xenograft model also proved that selenite could alter JNK activity, destroy microtubule structure and inhibit cell division in vivo. Moreover, TP53, MAPT and YWHAZ were identified to be three most confident interactors that link JNK to microtubule assembly using PPIs analysis. Our study indicated that cytosolic JNK-dependent microtubule re-organization took a protective function during selenite-induced apoptosis, while inhibition of this process would finally enhance the anti-tumor effect of selenite.
Sections du résumé
BACKGROUND
BACKGROUND
Selenite at high dosage exhibits great potential in curing tumors. It has been shown that selenite inhibits tumor growth through regulation of microtubule dynamics, however, the exact underlying mechanisms remained to be fully elucidated.
METHODS & RESULTS
RESULTS
Western blots were carried out to evaluate expression level of different molecules. Our current study discovered that selenite induced microtubule disassembly, cell cycle arrest and finally resulted in apoptosis in Jurkat leukemia cells, while during this process disassembled tubulins were re-organized after long-term exposure to selenite. Furthermore, JNK was activated in the cytoplasm of selenite-treated Jurkat cells, and inhibition of JNK activity successfully prevented the process of microtubule re-assembly. Moreover, inactivation of JNK further enhanced selenite-induced cell cycle arrest and apoptosis. According to the results from cell counting-8 assay, blockage of microtubule re-assembly by colchicine further inhibited Jurkat cell viability after exposure to selenite. Experiments in a xenograft model also proved that selenite could alter JNK activity, destroy microtubule structure and inhibit cell division in vivo. Moreover, TP53, MAPT and YWHAZ were identified to be three most confident interactors that link JNK to microtubule assembly using PPIs analysis.
CONCLUSION
CONCLUSIONS
Our study indicated that cytosolic JNK-dependent microtubule re-organization took a protective function during selenite-induced apoptosis, while inhibition of this process would finally enhance the anti-tumor effect of selenite.
Identifiants
pubmed: 37224747
pii: S0946-672X(23)00090-1
doi: 10.1016/j.jtemb.2023.127214
pii:
doi:
Substances chimiques
Selenious Acid
F6A27P4Q4R
JNK Mitogen-Activated Protein Kinases
EC 2.7.11.24
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
127214Informations de copyright
Copyright © 2023 Elsevier GmbH. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest Authors have no conflict interests.