B4 suppresses lymphoma progression by inhibiting fibroblast growth factor binding protein 1 through intrinsic apoptosis.

Autor:	Varier KM; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China.; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China., Dan G; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China., Li X; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China., Liu W; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China.; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China., Jiang F; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China., Linghu KG; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China., Li Y; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China.; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China., Ben-David Y; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China.; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China., Zhang N; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China., Xiao C; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China., Gajendran B; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China.; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China., Shen X; School of Pharmaceutical Sciences, Guizhou Medical University, Guiyang, China.; State Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang, China.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2024 Jun 28; Vol. 15, pp. 1408389. Date of Electronic Publication: 2024 Jun 28 (Print Publication: 2024).
DOI:	10.3389/fphar.2024.1408389
Abstrakt:	Lymphoma positions as the fifth most common cancer, in the world, reporting remarkable deaths every year. Several promising strategies to counter this disease recently include utilizing small molecules that specifically target the lymphoma cellular proteins to overwhelm its progression. FGFBP1 is a soluble intracellular protein that progresses cancer cell proliferation and is upregulated in several cancers. Therefore, inhibiting FGFBP1 could significantly slow down lymphoma progression through triggering apoptosis. Thus, in this study, a flavonoid B4, isolated from Cajanus cajan , has been investigated for its effects of B4 on lymphoma, specifically as an FGFBP1 inhibitor. B4 could selectively hinder the growth of lymphoma cells by inducing caspase-dependent intrinsic apoptosis through G 1 /S transition phase cell cycle arrest. RNA sequencing analysis revealed that B4 regulates the genes involved in B-cell proliferation and DNA replication by inhibiting FGFBP1 in vitro . B4 increases the survival rate of lymphoma mice. B4 also represses the growth of patient-derived primary lymphoma cells through FGFBP1 inhibition. Drug affinity responsive target stability experimentations authorize that B4 powerfully binds to FGFBP1. The overexpression of FGFBP1 raises the pharmacological sensitivity of B4, supplementing its specific action on lymphoma cells. This study pioneers the estimation of B4 as a possible anticancer agent for lymphoma treatment. These outcomes highlight its selective inhibitory effects on lymphoma cell growth by downregulating FGFBP1 expression through intrinsic apoptosis, causing mitochondrial and DNA damage, ultimately leading to the inhibition of lymphoma progression. These suggest B4 may be a novel FGFBP1 inhibitor for the lymphoma treatment. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2024 Varier, Dan, Li, Liu, Jiang, Linghu, Li, Ben-David, Zhang, Xiao, Gajendran and Shen.)
Databáze:	MEDLINE
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