Loganetin Inhibits Lymphoma Cell Proliferation and Promotes Apoptosis via Inactivating the Wnt/β-Catenin Pathway

Abstract

Background: Loganein, the primary active ingredient of Cornus officinalis, has been recognized for its anti-tumor effects in many cancer types, exerting an inhibitory effect on the Wnt/β-catenin pathway. However, its precise impact and underlying mechanism in lymphoma progression are still unclear. This study aimed to investigate whether loganetin regulated lymphoma progression through the Wnt/β-catenin pathway. Methods: To explore the regulatory impact of loganetin on lymphoma progression, we divided lymphoma cells (Jurkat) into three groups: the Control group (treated with 0 μmol/L loganetin), the Loganetin group (treated with 40, 80, 160 μmol/L loganetin), and the Loganetin+LiCl group (treated with 20 mM Wnt/β-catenin signal activator LiCl and 160 μmol/L loganetin). Subsequently, we assessed Jurkat cell viability, cell cycle, and apoptosis rate to reveal the effect of loganetin and Wnt/β-catenin pathway activator on lymphoma cell growth using cell counting kit-8 (CCK-8) assay, TdT-mediated dUTP Nick-End Labeling (TUNEL) staining assay, and flow cytometry. Moreover, the protein levels of CyclinD1, P21, C-Caspase-3, β-catenin, and c-myc were examined employing RT-qPCR and western blot analysis. Results: With the increasing of loganetin concentration, Jurkat cell viability, CyclinD1, Bcl-2, β-catenin, and c-myc levels were gradually decreased (p < 0.05), while the G0/G1 ratio, P21 level, cell apoptosis rate, TUNEL positive cell rate, as well as the levels of Fas, FASL, Bax and C-Caspase-3/total-caspase 3 were gradually improved (p < 0.05). Compared to the Loganetin group, Jurkat cell viability, CyclinD1, Bcl-2, β-catenin and c-myc levels were enhanced (p < 0.05), while the G0/G1 ratio, P21 level, cell apoptosis rate, TUNEL positive cell rate, Fas, FASL, Bax and C-Caspase-3/total-caspase 3 levels were reduced in the Loganetin+LiCl group (p < 0.05). Conclusions: Loganetin inactivated the Wnt/β-catenin pathway to restrain lymphoma cell proliferation and promote apoptosis.