A New Indole Derivative, LWX-473, Overcomes Glucocorticoid Resistance in Jurkat Cells by Activating Mediators of Apoptosis.

Autor:	Song J; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, 550014 Guiyang, Guizhou, China.; Natural Products Research Center of Guizhou Province, 550014 Guiyang, Guizhou, China.; School of Basic Medicine, Guizhou Medical University, 550025 Guiyang, Guizhou, China., Yang K; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, 550014 Guiyang, Guizhou, China.; Natural Products Research Center of Guizhou Province, 550014 Guiyang, Guizhou, China.; School of Pharmaceutical Sciences, Guizhou Medical University, 550025 Guiyang, Guizhou, China.; Department of Pharmacy, Guizhou Provincial People's Hospital, 550002 Guiyang, Guizhou, China., Gajendran B; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, 550014 Guiyang, Guizhou, China.; Natural Products Research Center of Guizhou Province, 550014 Guiyang, Guizhou, China.; School of Pharmaceutical Sciences, Guizhou Medical University, 550025 Guiyang, Guizhou, China., Varier KM; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, 550014 Guiyang, Guizhou, China.; Natural Products Research Center of Guizhou Province, 550014 Guiyang, Guizhou, China.; School of Pharmaceutical Sciences, Guizhou Medical University, 550025 Guiyang, Guizhou, China., Li W; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, 550014 Guiyang, Guizhou, China.; Natural Products Research Center of Guizhou Province, 550014 Guiyang, Guizhou, China., Liu Q; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, 550014 Guiyang, Guizhou, China.; Natural Products Research Center of Guizhou Province, 550014 Guiyang, Guizhou, China.; School of Pharmaceutical Sciences, Guizhou Medical University, 550025 Guiyang, Guizhou, China., Rao Q; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, 550014 Guiyang, Guizhou, China.; Natural Products Research Center of Guizhou Province, 550014 Guiyang, Guizhou, China., Hang Y; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, 550014 Guiyang, Guizhou, China.; Natural Products Research Center of Guizhou Province, 550014 Guiyang, Guizhou, China., Shen X; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, 550014 Guiyang, Guizhou, China.; Natural Products Research Center of Guizhou Province, 550014 Guiyang, Guizhou, China.; School of Pharmaceutical Sciences, Guizhou Medical University, 550025 Guiyang, Guizhou, China., Liu S; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, 550014 Guiyang, Guizhou, China.; Natural Products Research Center of Guizhou Province, 550014 Guiyang, Guizhou, China., Huang L; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, 550014 Guiyang, Guizhou, China.; Natural Products Research Center of Guizhou Province, 550014 Guiyang, Guizhou, China., Xu M; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, 550014 Guiyang, Guizhou, China.; Natural Products Research Center of Guizhou Province, 550014 Guiyang, Guizhou, China., Li Y; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, 550014 Guiyang, Guizhou, China.; Natural Products Research Center of Guizhou Province, 550014 Guiyang, Guizhou, China.
Jazyk:	angličtina
Zdroj:	Frontiers in bioscience (Landmark edition) [Front Biosci (Landmark Ed)] 2024 Apr 23; Vol. 29 (4), pp. 163.
DOI:	10.31083/j.fbl2904163
Abstrakt:	Background: Glucocorticoids (GCs) are commonly used as the primary chemotherapy for lymphoid malignancies, including acute lymphoblastic leukemia (ALL). However, the development of GC resistance limits their prolonged use. Methods: In this study, we investigated the potential of a newly synthesized indole derivative called LWX-473, in combination with the classic GC Dexamethasone (DEX), to enhance the responsiveness of Jurkat cells to GC treatment. Results: Our findings demonstrate that LWX-473 alone or in combination with DEX significantly improves GC-induced cell apoptosis and arrests the cell cycle in the G1 phase. Notably, the combination of LWX-473 and DEX exhibits superior efficacy in killing Jurkat cells compared to LWX-473 alone. Importantly, this compound demonstrates reduced toxicity towards normal cells. Conclusions: Our study reveals that LWX-473 has the ability to restore the sensitivity of Jurkat cells to DEX by modulating the mitochondrial membrane potential, activating the expression of DEX-liganded glucocorticoid receptor (GR), and inhibiting key molecules in the JAK/STAT signaling pathway. These findings suggest that LWX-473 could be a potential therapeutic agent for overcoming GC resistance in lymphoid malignancies. Competing Interests: The authors declare no conflict of interest. (© 2024 The Author(s). Published by IMR Press.)
Databáze:	MEDLINE
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