B细胞淋巴瘤来源于B细胞的多样分化阶段，是最常见的非霍奇金淋巴瘤，治疗面临巨大挑战，并且临床疗效不尽人意。黄烷酮类化合物黄烷酮B (FKB)，是从咖啡椰子中提取的天然黄酮，具有潜在的抗癌活性。然而，有关FKB对血液恶性肿瘤，特别是淋巴瘤的影响的证据仍然很少。本研究旨在调查FKB对淋巴瘤的抗肿瘤效果及其潜在机制。通过细胞增殖实验、流式细胞术和Western blotting 方法，确定FKB对B细胞淋巴瘤细胞系的影响及其作用机制。建立异种移植小鼠模型评估FKB的抗淋巴瘤疗效。FKB剂量和时间依赖性地降低了一系列B细胞淋巴瘤细胞系的存活率。FKB显著诱导线粒体凋亡，表现为增加的A型粘附素阳性细胞比例、线粒体膜电位丧失和caspase-3 和PARP的裂解。此外，FKB 抑制了BCL-XL表达并与BCL-2抑制剂ABT-199 协同作用。从机制上讲，FKB的处理降低了Akt、哺乳动物雷帕霉素靶蛋白(mTOR)、糖原合成酶激酶-3β (GSK3β)和核糖体蛋白S6(RPS6)的磷酸化。磷脂酰肌醇3-激酶(PI3K)、Akt或GSK3β的药物阻断增强了FKB的活性，表明PI3K/Akt级联在FKB介导的抑制作用中起到了作用。在小鼠异种移植模型中，FKB的腹腔注射明显减少了淋巴瘤的生长，伴随着肿瘤组织分裂和Ki-67阳性细胞的减少。我们的数据表明，FKB在B细胞淋巴瘤治疗中具有强大的治疗潜力。版权所有 © 2023 Elsevier GmbH。保留所有权利。

B-cell lymphoma, which originates from B cells at diverse differentiation stages, is the most common non-Hodgkin lymphoma with tremendous treatment challenges and unsatisfactory clinical outcomes. Flavokawain B (FKB), a naturally occurring chalcone extracted from kava, possesses promising anticancer properties. However, evidence on the effects of FKB on hematological malignancies, particularly lymphomas, remains scarce.This study aimed to investigate the antilymphoma effect of FKB and its underlying mechanisms.Proliferation assays, flow cytometry, and western blotting were employed to determine whether and how FKB affected B-cell lymphoma cell lines in vitro. Xenograft mouse models were established to evaluate the antilymphoma efficacy of FKB in vivo.FKB reduced the viability of a panel of B-cell lymphoma cell lines in a dose- and time-dependent manner. Mitochondrial apoptosis was markedly induced by FKB, as evidenced by an increased percentage of annexin V-positive cells, a loss of mitochondrial membrane potential, and cleavage of caspase-3 and PARP. Moreover, FKB inhibited BCL-XL expression and synergized with the BCL-2 inhibitor ABT-199. Mechanistically, FKB treatment decreased the phosphorylation of Akt, mammalian target of rapamycin (mTOR), glycogen synthase kinase-3β (GSK3β), and ribosomal protein S6 (RPS6). Pharmacological blockage of phosphoinositide 3-kinase (PI3K), Akt, or GSK3β potentiated the activity of FKB, indicating the involvement of the PI3K/Akt cascade in FKB-mediated inhibitory effects. In mouse xenograft models, the intraperitoneal administration of FKB significantly decreased lymphoma growth, accompanied by diminished mitosis and Ki-67 staining of tumor tissues.Our data demonstrate the robust therapeutic potential of FKB in the treatment of B-cell lymphoma.Copyright © 2023 Elsevier GmbH. All rights reserved.