The active ingredient β-sitosterol in Ganoderma regulates CHRM2-mediated aerobic glycolysis to induce apoptosis of lung adenocarcinoma cells.

IF 1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Genes & genetic systems Pub Date : 2025-04-05 Epub Date: 2024-11-14 DOI:10.1266/ggs.24-00108
Qiong Zhao, Yuting Pan, Danjia Zhang, Xiaolian Zhou, Liangyun Sun, Zihan Xu, Yunting Zhang
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引用次数: 0

Abstract

β-sitosterol is a natural plant steroidal compound with anti-cancer properties against various tumors. This work explored the inhibitory effect of β-sitosterol on the progression of lung adenocarcinoma (LUAD) and further analyzed its targets. We applied network pharmacology to obtain the components and targets of Ganoderma spore powder. The biological functions of β-sitosterol and CHRM2 were studied using the homograft mouse model and a series of in vitro experiments involving quantitative reverse transcription polymerase chain reaction, western blot, CCK-8, flow cytometry, immunohistochemistry and immunofluorescence. The regulatory influence of β-sitosterol on the glycolysis pathway was validated by measuring glucose consumption and lactate production, as well as the extracellular acidification rate and oxygen consumption rate. We found that CHRM2 binds directly to β-sitosterol. In vitro, CHRM2 overexpression repressed the apoptosis rate and expression of apoptosis-related proteins in LUAD cells, and promoted glycolysis, while the addition of lonidamine attenuated the apoptosis-inhibiting effect conferred by CHRM2 overexpression. Furthermore, β-sitosterol hindered glycolysis as well as the growth of tumors in vitro and in vivo. CHRM2 overexpression reversed the effect of β-sitosterol on the biological behavior of LUAD cells. Our results emphasize that CHRM2 is a direct target of β-sitosterol in LUAD cells. β-sitosterol can repress the glycolysis pathway, exerting an anti-tumor effect. These findings provide new support for the use of β-sitosterol as a therapeutic agent for LUAD.

灵芝中的活性成分β-谷甾醇能调节CHRM2介导的有氧糖酵解,从而诱导肺腺癌细胞凋亡。
背景:β-谷甾醇是一种天然植物甾体化合物,对多种肿瘤具有抗癌作用。本研究试图探讨β-谷甾醇对肺腺癌(LUAD)进展的抑制作用,并进一步分析其作用靶点:本研究应用网络药理学方法获得了灵芝孢子粉的成分和靶点。采用同种移植小鼠模型和一系列体外实验,包括定量反转录聚合酶链反应(qRT-PCR)、免疫印迹(WB)、CCK-8、流式细胞术、免疫组织化学(IHC)和免疫荧光(IF)实验,研究了β-谷甾醇和CHRM2的生物学功能。通过检测葡萄糖消耗、乳酸生成以及细胞外酸化率(ECAR)和耗氧量(OCR),验证了β-谷甾醇对糖酵解途径的调控作用:在该项目中,我们发现 CHRM2 是一种直接与 β-谷甾醇结合的蛋白质。在体外,CHRM2的过表达抑制了细胞凋亡率和细胞凋亡相关蛋白的表达,促进了糖酵解,而添加lonidamine则减弱了CHRM2过表达对LUAD细胞凋亡的抑制作用。此外,β-谷甾醇还能阻碍糖酵解以及体外和体内肿瘤的生长。CHRM2的过表达逆转了β-谷甾醇对LUAD细胞生物学行为的影响:结论:我们的项目强调了CHRM2是β-谷甾醇在LUAD细胞中的直接靶点。β-谷甾醇可抑制糖酵解途径,发挥抗肿瘤作用。这些发现为β-谷甾醇作为LUAD治疗药物的潜在用途提供了新的证据。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Genes & genetic systems
Genes & genetic systems 生物-生化与分子生物学
CiteScore
1.50
自引率
0.00%
发文量
22
审稿时长
>12 weeks
期刊介绍: Genes & Genetic Systems , formerly the Japanese Journal of Genetics , is published bimonthly by the Genetics Society of Japan.
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