The Effects of Cinobufagin on Hepatocellular Carcinoma Cells Enhanced by MRT68921, an Autophagy Inhibitor.

IF 5.4 3区材料科学 Q2 CHEMISTRY, PHYSICAL

ACS Applied Energy Materials Pub Date : 2023-01-01 DOI:10.1142/S0192415X23500726

Zhongwei Xu, Jun Bao, Xiaohan Jin, Heng Li, Kaiyuan Fan, Zhidong Wu, Min Yao, Yan Zhang, Gang Liu, Dan Wang, Xiaoping Yu, Jia Guo, Ruicheng Xu, Qian Gong, Fengmei Wang, Jin Wang

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引用次数: 2

Abstract

Cinobufagin, a cardiotonic steroid derived from toad venom extracts, exhibits significant anticancer properties by inhibiting Na[Formula: see text]/K[Formula: see text]-ATPase in cancer cells. It is frequently used in clinical settings to treat advanced-stage cancer patients, improving their quality of life and survival time. However, its long-term use can result in multidrug resistance to other chemotherapy drugs, and the exact mechanism underlying this effect remains unknown. Therefore, this study explores the molecular mechanism underlying the anticancer effects of cinobufagin in hepatocellular carcinomas (HCCs), specifically in HepG2 and Huh-7 cells. As determined using transcriptome analysis, cinobufagin-triggered protective autophagy suppressed cell apoptosis in liver cancer HepG2 and Huh-7 cells by inhibiting the phosphoinositide-3-Kinase (PI3K)-AKT serine/threonine kinase (AKT)-mammalian target of rapamycin (mTOR) pathway. Cinobufagin-inhibited cell proliferation, induced apoptosis, and generated cell autophagy by upregulating the expression of MAP1 light chain 3 protein II, Beclin1, and autophagy-related protein 12-5. In addition, the autophagy inhibitor MRT68921 improved the antiproliferative and proapoptotic effects of cinobufagin in the studied cell lines. Overall, this study suggests that combining cinobufagin with an autophagy inhibitor can effectively treat HCC, providing a potential strategy for cancer therapy.

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Cinobufagin对自噬抑制剂MRT68921增强肝癌细胞的作用

Cinobufagin是一种从蟾蜍毒液提取物中提取的强心剂类固醇，通过抑制癌细胞中的Na[公式:见文]/K[公式:见文]- atp酶，显示出显著的抗癌特性。它经常用于临床治疗晚期癌症患者，提高他们的生活质量和生存时间。然而，它的长期使用可能导致对其他化疗药物的多药耐药，而这种作用的确切机制尚不清楚。因此，本研究探讨了蟾毒蛋白在肝细胞癌(hcc)，特别是HepG2和Huh-7细胞中的抗癌作用的分子机制。转录组分析表明，cinobufagin触发的保护性自噬通过抑制磷酸肌醇-3-激酶(PI3K)-AKT丝氨酸/苏氨酸激酶(AKT)-哺乳动物雷帕霉素靶蛋白(mTOR)通路抑制肝癌HepG2和hh -7细胞的细胞凋亡。cinobufagin通过上调MAP1轻链3蛋白II、Beclin1和自噬相关蛋白12-5的表达，抑制细胞增殖，诱导细胞凋亡，产生细胞自噬。此外，自噬抑制剂MRT68921在研究的细胞系中增强了蟾毒蛋白的抗增殖和促凋亡作用。综上所述，本研究提示cinobufagin联合自噬抑制剂可有效治疗HCC，为癌症治疗提供了一种潜在的策略。

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

ACS Applied Energy Materials Materials Science-Materials Chemistry

CiteScore

10.30

自引率

6.20%

发文量

1368

期刊介绍： ACS Applied Energy Materials is an interdisciplinary journal publishing original research covering all aspects of materials, engineering, chemistry, physics and biology relevant to energy conversion and storage. The journal is devoted to reports of new and original experimental and theoretical research of an applied nature that integrate knowledge in the areas of materials, engineering, physics, bioscience, and chemistry into important energy applications.