淋巴瘤是世界上第五大常见癌症，每年都有大量死亡病例报告。最近对抗这种疾病的几种有前景的策略包括利用专门针对淋巴瘤细胞蛋白的小分子来抑制其进展。 FGFBP1 是一种可溶性细胞内蛋白，可促进癌细胞增殖，并在多种癌症中表达上调。因此，抑制 FGFBP1 可以通过触发细胞凋亡来显着减缓淋巴瘤的进展。因此，在这项研究中，研究了从木豆中分离出的类黄酮 B4 对淋巴瘤的影响，特别是作为 FGFBP1 抑制剂。 B4 可通过 G1/S 过渡期细胞周期阻滞诱导 caspase 依赖性内在凋亡，选择性阻碍淋巴瘤细胞的生长。 RNA 测序分析表明，B4 在体外通过抑制 FGFBP1 来调节参与 B 细胞增殖和 DNA 复制的基因。 B4 可以提高淋巴瘤小鼠的存活率。 B4 还通过抑制 FGFBP1 来抑制源自患者的原发性淋巴瘤细胞的生长。药物亲和力响应靶标稳定性实验证实 B4 与 FGFBP1 强有力地结合。 FGFBP1 的过度表达提高了 B4 的药理敏感性，补充了其对淋巴瘤细胞的特异性作用。这项研究开创了将 B4 作为淋巴瘤治疗的可能抗癌药物的估计。这些结果凸显了其通过内在细胞凋亡下调 FGFBP1 表达，引起线粒体和 DNA 损伤，最终抑制淋巴瘤进展，从而对淋巴瘤细胞生长具有选择性抑制作用。这些表明 B4 可能是一种用于淋巴瘤治疗的新型 FGFBP1 抑制剂。版权所有 © 2024 Varier、Dan、Li、Liu、Jiang、Linghu、Li、Ben-David、Zhang、Xiao、Gajendran 和 Shen。

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 G1/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.Copyright © 2024 Varier, Dan, Li, Liu, Jiang, Linghu, Li, Ben-David, Zhang, Xiao, Gajendran and Shen.