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毛花洋地黄苷 C，一种强心苷，通过蛋白激酶 Cδ 发挥作用，导致人肝癌细胞凋亡。

Lanatoside C, a cardiac glycoside, acts through protein kinase Cδ to cause apoptosis of human hepatocellular carcinoma cells.

机构信息

The Ph.D. Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan.

Division of Industrial Promotion, Development Center for Biotechnology, Taipei, Taiwan.

出版信息

Sci Rep. 2017 Apr 7;7:46134. doi: 10.1038/srep46134.

DOI:10.1038/srep46134
PMID:28387249
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5384006/
Abstract

Recent studies have revealed that cardiac glycosides, such as digitalis and digoxin, have anticancer activity and may serve as lead compounds for the development of cancer treatments. The poor prognosis of hepatocellular carcinoma (HCC) patients reflects the development of resistance to current chemotherapeutic agents, highlighting the need for discovering new small-molecule therapeutics. Here, we found that lanatoside C, an anti-arrhythmic agent extracted from Digitalis lanata, inhibited the growth of HCC cells and dramatically decreased tumor volume as well as delayed tumor growth without obvious body weight loss. Moreover, lanatoside C triggered mitochondrial membrane potential (MMP) loss, activation of caspases and translocation of apoptosis-inducing factor (AIF) into the nucleus, which suggests that lanatoside C induced apoptosis through both caspase-dependent and -independent pathways. Furthermore, we discovered that lanatoside C activated protein kinase delta (PKCδ) via Thr505 phosphorylation and subsequent membrane translocation. Inhibition of PKCδ reversed lanatoside C-induced MMP loss and apoptosis, confirming that lanatoside C caused apoptosis through PKCδ activation. We also found that the AKT/mTOR pathway was negatively regulated by lanatoside C through PKCδ activation. In conclusion, we provide the first demonstration that the anticancer effects of lanatoside C are mainly attributable to PKCδ activation.

摘要

最近的研究表明，洋地黄毒苷等强心苷具有抗癌活性，可能成为开发癌症治疗方法的先导化合物。肝癌 (HCC) 患者的预后不良反映了对现有化疗药物的耐药性的发展，这凸显了发现新的小分子治疗方法的必要性。在这里，我们发现从毛地黄中提取的抗心律失常药毛地黄毒苷 C 抑制 HCC 细胞的生长，并显著降低肿瘤体积和延迟肿瘤生长而无明显体重减轻。此外，毛地黄毒苷 C 触发线粒体膜电位 (MMP) 丧失、半胱天冬酶的激活和凋亡诱导因子 (AIF) 向核内易位，这表明毛地黄毒苷 C 通过半胱天冬酶依赖性和非依赖性途径诱导细胞凋亡。此外，我们发现毛地黄毒苷 C 通过 Thr505 磷酸化和随后的膜易位激活蛋白激酶 δ (PKCδ)。PKCδ 抑制剂逆转了毛地黄毒苷 C 诱导的 MMP 丧失和凋亡，证实了毛地黄毒苷 C 通过 PKCδ 激活诱导凋亡。我们还发现 AKT/mTOR 途径通过 PKCδ 激活被毛地黄毒苷 C 负调控。总之，我们首次证明毛地黄毒苷 C 的抗癌作用主要归因于 PKCδ 的激活。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f2/5384006/ac60564706cb/srep46134-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f2/5384006/c591e6edee5a/srep46134-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f2/5384006/da2b7be73afa/srep46134-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f2/5384006/d96ce04fb3cc/srep46134-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f2/5384006/571c4b73144e/srep46134-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f2/5384006/5d40d4ff1ed7/srep46134-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f2/5384006/ac60564706cb/srep46134-f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f2/5384006/c591e6edee5a/srep46134-f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f2/5384006/da2b7be73afa/srep46134-f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f2/5384006/d96ce04fb3cc/srep46134-f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f2/5384006/571c4b73144e/srep46134-f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f2/5384006/5d40d4ff1ed7/srep46134-f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/81f2/5384006/ac60564706cb/srep46134-f6.jpg

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2
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CA Cancer J Clin. 2016 Jan-Feb;66(1):7-30. doi: 10.3322/caac.21332. Epub 2016 Jan 7.
3
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使用细胞绘画图像数据进行生物活性预测的半监督对比学习
J Chem Inf Model. 2025 Jan 27;65(2):528-543. doi: 10.1021/acs.jcim.4c00835. Epub 2025 Jan 6.
4
Targeting the mTOR Pathway in Hepatocellular Carcinoma: The Therapeutic Potential of Natural Products.靶向肝细胞癌中的mTOR信号通路：天然产物的治疗潜力
J Inflamm Res. 2024 Dec 6;17:10421-10440. doi: 10.2147/JIR.S501270. eCollection 2024.
5
Drug Repurposing for Cancer Treatment: A Comprehensive Review.药物重用于癌症治疗：全面综述。
Int J Mol Sci. 2024 Nov 19;25(22):12441. doi: 10.3390/ijms252212441.
6
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Molecules. 2024 Feb 16;29(4):877. doi: 10.3390/molecules29040877.
7
Current trends and future prospects of drug repositioning in gastrointestinal oncology.胃肠道肿瘤药物重新定位的当前趋势与未来前景
Front Pharmacol. 2024 Jan 4;14:1329244. doi: 10.3389/fphar.2023.1329244. eCollection 2023.
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5
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6
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