Anti-liver cancer therapeutic targets and safety of usenamine A in experimental liver cancer.

IF 2.8 4区医学 Q2 PHARMACOLOGY & PHARMACY

Journal of Pharmacy and Pharmacology Pub Date : 2025-01-06 DOI:10.1093/jpp/rgae096

Xiaoqiong He, Zhangping Zhou, Jing Wang, Qing Zhao, Shirui Fan, Qian Yao, Wenjing Lian, Yutong You

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引用次数: 0

Abstract

Background: Liver cancer is highly heterogeneous with poor drug response. Usenamine A has anticancer activity. Usnic acid has hepatocytotoxicity.

Objectives: As a derivative of usnic acid, if usenamine A can be safely used in treatment for liver cancer is unknown.

Methods: MTT and clone formation assays assessed cell viability and proliferation. Tumor growth was determined using a xenograft model. Flow cytometry was used to detect the cell cycle. mRNA transcriptome sequencing investigated differential gene expression. Safety was evaluated in mice.

Key findings: Usenamine A inhibited proliferation and clone formation of HepG2 cells and xenograft tumor growth through cell cycle arrest at G0/G1. Usenamine A altered gene expression in a direction supporting anticancer activity. IL24, JUN, DUSP4, and DUSP5 were upregulated while PRKACA, PRKCB, TP53, WNT6, E2F3, LGR4, GPR78, and MAPK4 were downregulated. Ten of above genes overlapped in the KEGG enriched non-small cell lung cancer/glioma/cytokine-cytokine receptor interaction/Wnt/MAPK pathway network. Usenamine A has a strong binding affinity for PRKACA and PRKCB proteins. Usenamine A showed minimal toxicity in mice.

Conclusions: Usenamine A is a safe anticancer agent against hepatocellular carcinoma. Regulation of 12 cancer-associated genes and the correlated pathway network are its therapeutic targets.

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在实验性肝癌中使用乌司那敏 A 的抗肝癌治疗靶点和安全性。

背景：肝癌具有高度异质性，对药物反应差。乌司那敏 A 具有抗癌活性。目的：作为鸟苷酸的衍生物，鸟苷酸 A 能否安全地用于肝癌治疗尚不清楚：目的：作为一种鸟苷酸衍生物，乌司那敏 A 能否安全地用于肝癌治疗尚不清楚：方法：MTT 和克隆形成试验评估细胞活力和增殖。采用异种移植模型确定肿瘤生长情况。mRNA 转录组测序研究了不同基因的表达。对小鼠进行了安全性评估：乌司那敏 A 通过细胞周期 G0/G1 期的停滞抑制了 HepG2 细胞的增殖和克隆形成以及异种移植肿瘤的生长。乌司那敏 A 改变了支持抗癌活性的基因表达。IL24、JUN、DUSP4 和 DUSP5 上调，而 PRKACA、PRKCB、TP53、WNT6、E2F3、LGR4、GPR78 和 MAPK4 下调。上述基因中有 10 个在 KEGG 富集的非小细胞肺癌/胶质瘤/细胞因子-细胞因子受体相互作用/Wnt/MAPK 通路网络中重叠。乌司那敏 A 与 PRKACA 和 PRKCB 蛋白有很强的结合亲和力。结论：Usenamine A对小鼠的毒性极小：结论：Usenamine A 是一种安全的肝细胞癌抗癌剂。结论：Usenamine A 是一种安全的肝癌抗癌剂，其治疗靶点是 12 个癌症相关基因的调控和相关通路网络。

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

Journal of Pharmacy and Pharmacology 医学-药学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

3 months

期刊介绍： JPP keeps pace with new research on how drug action may be optimized by new technologies, and attention is given to understanding and improving drug interactions in the body. At the same time, the journal maintains its established and well-respected core strengths in areas such as pharmaceutics and drug delivery, experimental and clinical pharmacology, biopharmaceutics and drug disposition, and drugs from natural sources. JPP publishes at least one special issue on a topical theme each year.