Scutebarbatine B通过多种途径诱导细胞周期阻滞和凋亡发挥抗乳腺癌活性。

IF 6.3 2区 医学 Q1 CHEMISTRY, MEDICINAL
Chong Niu, Ruo-Tong Li, Xiao-Shan Hao, Xiao Qi, Feng-Ze Wang, Hong-Rong Fei
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引用次数: 0

摘要

乳腺癌是死亡率高的妇女中最常见的癌症。确定有效的抗癌化合物以提高总体生存率是必要的。本研究旨在探讨从半边黄芩中提取的二萜类生物碱半边黄芩碱B (SBT-B)对乳腺癌的作用及其机制。通过细胞活力测定、5-乙基-2′-脱氧尿苷(EdU)测定、免疫荧光、流式细胞术分析、tdt介导的dutp -生物素刻针末端标记(TUNEL)染色、Western blot分析、2′,7′-二氯双氢荧光素(DCFH-DA)、双氢乙啶(DHE)染色等方法探讨SBT-B的体外抗癌机制。采用小鼠异种移植物模型在体内评价其抗癌特性。我们证明了SBT-B以剂量依赖的方式抑制乳腺癌细胞的增殖。SBT-B处理诱导DNA损伤反应,G2/M期阻滞,下调cyclinB1、cyclinD1、Cdc2和p-Cdc2的表达。SBT-B可通过增加乳腺癌细胞中caspase-8、caspase-9和PARP的裂解而引发细胞凋亡。此外,SBT-B增加了细胞内活性氧(ROS)的产生。用活性氧清除剂n -乙酰半胱氨酸(NAC)处理部分阻断了SBT-B诱导的caspase-8和PARP的活性降低和裂解。此外,SBT-B阻断了pRB/E2F1和Akt/mTOR通路。与SBT-B孵育可增加IRE1和phospho-JNK的表达。在体内,SBT-B在异种移植模型中表现出明显的肿瘤生长抑制作用。我们首次证明SBT-B在乳腺癌细胞中诱导DNA损伤、细胞周期阻滞和细胞凋亡。在SBT-B的抗癌活性中,ROS的产生、致癌信号的抑制和IRE1/JNK通路的激活发挥了重要作用。我们的研究强调了SBT-B作为治疗人类乳腺癌的替代候选药物的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Scutebarbatine B Exerts Anti-Breast Cancer Activity by Inducing Cell Cycle Arrest and Apoptosis Through Multiple Pathways.

Breast cancer is the most commonly occurring cancer among women with high mortality. Identifying effective anticancer compounds to improve the overall survival is imperative. The present study was designed to evaluate the effects and underlying mechanisms of Scutebarbatine B (SBT-B), a diterpenoid alkaloid extracted from Scutellaria barbata D. Don (S. barbata), on breast cancer. Cell viability assay, 5-ethynyl-2'-deoxyuridine (EdU) assay, immunofluorescence, flow cytometry analysis, TdT-mediated dUTP-biotin nick end labeling (TUNEL) staining, Western blot analysis, 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), and dihydroethidium (DHE) staining were performed to elucidate the anticancer mechanisms of SBT-B in vitro. Mice xenograft models were used to assess the anticancer properties in vivo. We demonstrated that SBT-B suppressed the proliferation of breast cancer cells in a dose-dependent manner. SBT-B treatment induced DNA damage response, G2/M phase arrest and downregulated the expression of cyclinB1, cyclinD1, Cdc2, and p-Cdc2. SBT-B could trigger apoptosis through increasing the cleavage of caspase-8, caspase-9 and PARP in breast cancer cells. Additionally, SBT-B elevated the generation of intracellular reactive oxygen species (ROS). Treatment with a ROS scavenger N-acetyl cysteine (NAC) partially blocked viability reduction and cleavage of caspase-8 and PARP induced by SBT-B. Moreover, SBT-B blocked pRB/E2F1 and Akt/mTOR pathways. Incubation with SBT-B increased the expression of IRE1 and phospho-JNK. In vivo, SBT-B exhibited significant suppression of tumor growth in xenograft models. We demonstrate firstly that SBT-B induces DNA damage, cell cycle arrest and apoptosis in breast cancer cells. ROS generation, suppression of oncogenic signaling and activation of IRE1/JNK pathway play an essential role in the anticancer activity of SBT-B. Our study highlights the potential of SBT-B as an alternative candidate to treat human breast cancer.

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来源期刊
Phytotherapy Research
Phytotherapy Research 医学-药学
CiteScore
12.80
自引率
5.60%
发文量
325
审稿时长
2.6 months
期刊介绍: Phytotherapy Research is an internationally recognized pharmacological journal that serves as a trailblazing resource for biochemists, pharmacologists, and toxicologists. We strive to disseminate groundbreaking research on medicinal plants, pushing the boundaries of knowledge and understanding in this field. Our primary focus areas encompass pharmacology, toxicology, and the clinical applications of herbs and natural products in medicine. We actively encourage submissions on the effects of commonly consumed food ingredients and standardized plant extracts. We welcome a range of contributions including original research papers, review articles, and letters. By providing a platform for the latest developments and discoveries in phytotherapy, we aim to support the advancement of scientific knowledge and contribute to the improvement of modern medicine.
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