Lobetyolin Suppresses the Proliferation of Hepatocellular Carcinoma through Activating DUSP1-ERK1/2 Signaling Pathway.

IF 1.7 4区 医学 Q3 PHARMACOLOGY & PHARMACY Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI:10.1248/bpb.b24-00307
Jixuan Hu, Dandan Wang, Feng Wang, Pingping Lin
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Abstract

Hepatocellular carcinoma (HCC) is the most prevalent primary liver cancer with limited treatment options. Lobetyolin (LBT), a polyacetylene glycoside mainly extracted from the roots of Codonopsis pilosula, has been reported to have anti-tumor efficancy in various cancers. However, the role of LBT as well as its underlying mechanisms in HCC remain unclear. Here we investigated the impact of LBT on the phenotype in HepG2 and Huh7 cells. We found that LBT significantly induced cell growth inhibition and mitochondria-dependent apoptosis in HCC cells. Moreover, LBT upregulated dual specificity phosphatase-1 (DUSP1) expression and knockingdown DUSP1 markedly attenuated those effects induce by LBT. Meanwhile, LBT decreased the phosphorylation level of extracellular signal-regulated kinase 1/2 (ERK1/2), a well-recognized downstream effector of DUSP1, and knockingdown DUSP1 partially recovered LBT-induced inactivation of ERK1/2. In conclusion, the present study indicated that LBT could induce cell death of HCC via promotion of DUSP1-mediated ERK1/2 inhibition. These data will help to establish the evidence of LBT to treat HCC.

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洛贝替林通过激活 DUSP1-ERK1/2 信号通路抑制肝细胞癌的增殖
肝细胞癌(HCC)是最常见的原发性肝癌,但治疗方法有限。据报道,Lobetyolin(LBT)是一种主要从党参根中提取的聚乙炔苷,在多种癌症中具有抗肿瘤功效。然而,LBT 在 HCC 中的作用及其内在机制仍不清楚。在此,我们研究了枸杞多糖对 HepG2 和 Huh7 细胞表型的影响。我们发现,LBT 能明显诱导 HCC 细胞的生长抑制和线粒体依赖性凋亡。此外,LBT 会上调双特异性磷酸酶-1(DUSP1)的表达,而敲除 DUSP1 会明显减轻 LBT 的诱导作用。同时,LBT降低了细胞外信号调节激酶1/2(ERK1/2)的磷酸化水平,ERK1/2是DUSP1公认的下游效应物,敲除DUSP1可部分恢复LBT诱导的ERK1/2失活。总之,本研究表明,LBT 可通过促进 DUSP1 介导的 ERK1/2 抑制作用诱导 HCC 细胞死亡。这些数据将有助于确立枸橼酸枸橼酸钠治疗 HCC 的证据。
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来源期刊
CiteScore
3.50
自引率
5.00%
发文量
247
审稿时长
2 months
期刊介绍: Biological and Pharmaceutical Bulletin (Biol. Pharm. Bull.) began publication in 1978 as the Journal of Pharmacobio-Dynamics. It covers various biological topics in the pharmaceutical and health sciences. A fourth Society journal, the Journal of Health Science, was merged with Biol. Pharm. Bull. in 2012. The main aim of the Society’s journals is to advance the pharmaceutical sciences with research reports, information exchange, and high-quality discussion. The average review time for articles submitted to the journals is around one month for first decision. The complete texts of all of the Society’s journals can be freely accessed through J-STAGE. The Society’s editorial committee hopes that the content of its journals will be useful to your research, and also invites you to submit your own work to the journals.
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