作者: Hahn, Dongyup ; Lee, Hong Jin ; Lee, Ga Yeon ; Son, Hui Mang ; Kwon, Jung Won ; Cao, Thao Quyen ; Kim, Jin Tae ; Kim, Jaewon ; Chi, Hae Na ; Zhou, Yimeng ; Qiu, Shuai

After confirmation of Arnebia euchroma by genetic analysis, we identified the key compounds from the root: alkannin (1), acetylalkannin (2), β-acetoxyisovaleryl alkannin (3), isobutyryl alkannin (4), and β,β-dimethylacryloyl alkannin (DMA) (5). Among these, DMA most effectively inhibited the proliferation of triple-negative breast cancer (TNBC) cells, with IC₅₀ values of 5.1 μM (MDA-MB-231) and 8.7 μM (MCF10DCIS.com). DMA and the Hedgehog (Hh) inhibitor Gant61 targeting Gli1 significantly induced apoptosis, as indicated by increased Bax and cleaved PARP, and decreased Bcl-2 levels (p < 0.01) in both cell lines. We also identified AKT as a potential target of DMA, as treatment reduced phosphorylated AKT (Ser473) protein levels by 66.3% ± 0.7% and 30.1% ± 5.7% in MDA-MB-231 and MCF10DCIS.com cells, respectively (p < 0.01). In vivo, DMA (25 mg/kg) suppressed MDA-MB-231 xenograft tumor growth by approximately 78% (p < 0.01) and induced apoptosis through regulating AKT/Hh/Gli1 axis. Interestingly, the reduced form of DMA (5') lost its efficacy in inhibiting proliferation, p-AKT expression, and Gli1 transcriptional activity and nuclear localization, indicating that the Michael acceptor in DMA is critical for inhibiting TNBC growth. Overall, DMA suppressed TNBC in vitro and in vivo through AKT/Gli1 pathway and shows potential as a potent agent against TNBC.

2025-05-01·PHYTOMEDICINE

Alkannin triggered apoptosis and ferroptosis in gastric cancer by suppressing lipid metabolism mediated by the c-Fos/SREBF1 axis

Article

作者: Zhao, Minghui ; Li, Kai ; Zhao, Gang ; Kou, Qiming ; Li, Siqi ; Chen, Hongbai ; Yu, Huayang ; Qu, Jie ; Qi, Yanyu ; Lu, Chenghong ; Li, Liang ; Li, Shan ; Li, Qin ; Yuan, Hang ; Lin, Ping ; Xiao, Hengyi ; Wang, Qijing ; Chen, Kang ; Wang, Guanru

BACKGROUND:

Gastric cancer (GC), one of the most common malignancies with high mortality worldwide, currently requires beneficial therapeutic strategies. Alkannin is the primary active component of Lithospermum erythrorhizon and has been shown to have potential anticancer effects on a variety of cancers. However, the specific effects and molecular mechanisms of alkannin against GC remain unknown.

PURPOSE:

This study aimed to explore the detailed role and downstream effectors of alkannin in the treatment of GC.

METHODS:

The functions of alkannin on the proliferation, migration and invasion of GC cells were measured via CCK-8, EdU, colony formation, LDH release, flow cytometry, wound healing, and Transwell assays. BODIPY-C11 staining, determination of cellular ferrous iron, MDA and GSH levels, and western blotting were used to evaluate alkannin-induced ferroptosis. Transcriptome sequencing was analyzed to identify differentially expressed genes. Nile red staining and cholesterol and triglyceride assays were utilized to examine changes in lipid metabolism. Transcriptional regulation was determined by real-time PCR, dual-luciferase reporter and chromatin immunoprecipitation assays. Finally, a xenograft animal model was employed to assess tumor growth in vivo.

RESULTS:

Alkannin inhibited growth and motility and simultaneously triggered apoptotic and ferroptotic cell death in GC cells. Transcriptome sequencing analysis revealed that alkannin treatment downregulated c-Fos expression. The overexpression of c-Fos conferred the GC cells to tolerate alkannin in vitro and in vivo. Moreover, we confirmed that c-Fos activated SREBF1 transcription by directly binding to TPA-responsive elements within the SREBF1 promoter, leading to increased expression of lipid biosynthesis-related genes, which counteracted ferroptosis through the maintenance of cellular lipid homeostasis.

CONCLUSION:

Our present study provides the first evidence that alkannin induces both apoptosis and ferroptosis in GC cells and reveals a novel mechanism by which alkannin restrains c-Fos-dependent SREBF1 transcriptional activation, leading to lipid metabolism and redox homeostasis disorders. Our findings highlight that alkannin is an available and promising natural product for the avoidance of drug resistance and the clinical treatment of GC.

2025-05-01·Chinese Journal of Natural Medicines

Comprehensive analysis of the antibacterial activity of 5,8-dihydroxy-1,4-naphthoquinone derivatives against methicillin-resistant Staphylococcus aureus

Article

作者: Wen, Zhongling ; Yang, Liu ; Li, Zhongyi ; Chen, Qingqing ; Wang, Changyi ; Lu, Guihua ; Ding, Yuhang ; Han, Hongwei ; Fazal, Aliya ; Lin, Hongyan ; Qi, Jinliang ; Yin, Tongming ; Zhang, Yahan ; Yang, Yonghua ; Chen, Xingyu ; Ma, Yudi

Given the increasing concern regarding antibacterial resistance, the antimicrobial properties of naphthoquinones have recently attracted significant attention. While 1,4-naphthoquinone and its derivatives have been extensively studied, the antibacterial properties of 5,8-dihydroxy-1,4-naphthoquinone derivatives remain relatively unexplored. This study presents a comprehensive in vitro and in vivo analysis of the antibacterial activity of 35 naturally sourced and chemically synthesized derivatives of 5,8-dihydroxy-1,4-naphthoquinone. Kirby-Bauer antibiotic testing identified three compounds with activity against methicillin-resistant Staphylococcus aureus (MRSA), with one compound (PNP-02) demonstrating activity comparable to vancomycin in minimum inhibitory concentration, minimum bactericidal concentration (MBC), and time-kill assays. Microscopic and biochemical analyses revealed that PNP-02 adversely affects the cell wall and cell membrane of MRSA. Mechanistic investigations, including proteomic sequencing analyses, Western blotting, and RT-qPCR assays, indicated that PNP-02 compromises cell membrane integrity by inhibiting arginine biosynthesis and pyrimidine metabolism pathways, thereby increasing membrane permeability and inducing bacterial death. In an in vivo mouse model of skin wound healing, PNP-02 exhibited antibacterial efficacy similar to vancomycin. The compound demonstrated low toxicity to cultured human cells and in hemolysis assays and remained stable during serum incubation. These findings suggest that PNP-02 possesses promising bioactivity against MRSA and represents a potential novel antibacterial agent.

项与 Alkannin 相关的新闻（医药）

2025-05-30

·今日头条

福医大攻克肝癌难题: 新策略实现"控生长+增敏感"双重疗效

【导读】过表达 LTβR 的嵌合抗原受体 T 细胞（CAR-T 细胞）在对抗实体瘤方面表现出惊人的效果，展现出强大的抗耗竭和增殖能力。然而，LTβR 在 CD4+ T 细胞分化和抗肿瘤活性中的作用仍不清楚。 5月28日，福建医科大学研究团队在期刊《Cell Death&Disease》上发表了题为“N-glycosylated LTβR increases the Th17/Treg cell ratio in liver cancer by blocking RORC ubiquitination and FOXP3 transcription”的研究论文，本研究中，研究人员采用原代或皮下移植的小鼠肝细胞癌（HCC）模型以及流式细胞术，研究了条件性敲入 LTβR 对 CD4+ T 细胞分化和反应的影响，特别是 Th17/Treg 细胞比例，以及其对 HCC 进展的影响。本研究结果表明，LTβR 的 N-糖基化可阻止 RORC 泛素化和 Foxp3 转录，提高 Th17/Treg 细胞比例，阻碍肝细胞癌的进展。 https://www.nature.com/articles/s41419-025-07738-2#Sec13 研究背景 01 LTβR 是肿瘤坏死因子受体超家族的一部分，是淋巴毒素的细胞表面受体，可触发细胞凋亡和细胞因子释放。它存在于多种非免疫细胞和髓系来源的免疫细胞上，但在淋巴细胞上很少。异位表达的 LTβR 可促进 T 细胞增殖，维持年轻、干细胞样 T 细胞特征，并防止其耗竭。虽然引入 LTβR 的 CAR-T 细胞表现出强大的细胞毒性和增殖能力，但其对 CD4+ T 细胞分化的影响仍需进一步研究。 Th17 细胞在肿瘤微环境（TME）中很常见，但其在肿瘤免疫中的作用存在争议。过度的 Th17 细胞介导的炎症会导致癌症，但过继转移研究表明小鼠的 Th17 细胞具有抗癌作用。它们在促进或抑制癌症方面的作用高度依赖于肿瘤类型。了解 Th17 细胞在肿瘤免疫中的作用对于癌症免疫疗法至关重要。此外，肿瘤中高含量的调节性 T 细胞（Treg 细胞）预示着不良预后，因为它们分泌的细胞因子有助于肿瘤免疫逃逸和生长。因此，探究 Th17 和 Treg 细胞分化背后的分子机制对于理解肿瘤微环境以及增强基于 T 细胞的抗肿瘤疗法至关重要。 LTβR 提高了糖酵解抑制剂的免疫治疗效果 02 早期的单细胞 RNA 测序数据表明，肝细胞癌（HCC）细胞的糖酵解/糖异生途径得分最高。研究人员假设 HCC 细胞中的糖酵解会降低微环境中的葡萄糖水平，从而破坏由 LTβR N-糖基化维持的 Th17/Treg 细胞比例平衡。体内研究表明，这些酶会阻碍 Th17 细胞浸润并提高 Treg 细胞水平。然而，CD4+ T 细胞中的 Ltbr-cKI 并未抵消这一现象，这表明 LTβR 在 Th17/Treg 细胞比例平衡中的作用取决于充足的葡萄糖。为了探究 LTβR 在临床前模型中的作用是否适用于患者的 HCC 以及它是否能提高免疫治疗中糖酵解抑制剂的敏感性，研究人员创建了患者来源的原位异种移植（PDOX）模型，并用两种 FDA 批准的糖酵解抑制剂进行治疗：Alkannin（PKM2 抑制剂）和 WZB117（GLUT1 抑制剂）。此外，研究人员使用 Ark313 特异性过表达 LTβR 在人类 CD4+ T 细胞中，以测试 LTβR 是否能提高药物的效果。这两种药物和 LTβR 过表达均抑制了 HCC 的生长，并提高了 Th17/Treg 细胞比例。同时，LTβR 增强了 Alkannin 对 IFNG/RORC 促进以及对调节性 T 细胞抑制的作用，并增强了 WZB117 对 IFNG/RORC 促进的作用。这两种抑制剂还促进了 LTβR 的 Th17 细胞浸润。结论 03 总之，本研究证明，N-糖基化的 LTβR 抑制了肝细胞癌（HCC）的进展，并通过提高 Th17/Treg 细胞的比例增强了对糖酵解抑制剂抗癌作用的敏感性。参考资料： https://www.nature.com/articles/s41419-025-07738-2#Sec13 【关于投稿】转化医学网（360zhyx.com）是转化医学核心门户，旨在推动基础研究、临床诊疗和产业的发展，核心内容涵盖组学、检验、免疫、肿瘤、心血管、糖尿病等。如您有最新的研究内容发表，欢迎联系我们进行免费报道（公众号菜单栏-在线客服联系），我们的理念：内容创造价值，转化铸就未来！转化医学网（360zhyx.com）发布的文章旨在介绍前沿医学研究进展，不能作为治疗方案使用；如需获得健康指导，请至正规医院就诊。责任声明：本稿件如有错误之处，敬请联系转化医学网客服进行修改事宜！微信号：zhuanhuayixue 热门推荐活动点击免费报名 🕓 上海｜2025年6月12-15日 ▶ 第七届上海国际癌症大会暨第十八届全国医学生物技术研讨会暨第六届中德双边论坛 🕓 上海｜2025年7月17-18日 ▶ 第四届长三角体外诊断产业高峰论坛 🕓 北京｜2025年9月19-20日 ▶ 第六届单细胞技术应用研讨会暨空间组学前沿研讨会 🕓 上海｜2025年11月14-15日 ▶ 第二届中国类器官转化医学大会点击对应文字查看详情

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100 项与 Alkannin 相关的药物交易

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