Salvia chinensis Benth Inhibits Triple-Negative Breast Cancer Progression by Inducing the DNA Damage Pathway.
Salvia chinensis Benth Inhibits Triple-Negative Breast Cancer Progression by Inducing the DNA Damage Pathway.
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丹参通过诱导 DNA 损伤途径抑制三阴性乳腺癌进展
DOI：
10.3389/fonc.2022.882784
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发表时间：
2022
影响因子：
4.7
通讯作者：
中科院分区：
文献类型：
--
作者：
Triple-negative breast cancer (TNBC) is distinguished by early recurrence and metastases, a high proclivity for treatment resistance, and a lack of targeted medicines, highlighting the importance of developing innovative therapeutic techniques. Salvia chinensis Benth (SCH) has been widely studied for its anticancer properties in a variety of cancers. However, its significance in TNBC treatment is rarely discussed. Our study investigated the anticancer effect of SCH on TNBC and the underlying mechanisms. First, we used clonogenic, cell viability, flow cytometry, and Transwell assays to assess the effect of SCH on TNBC. Bioinformatic studies, especially network pharmacology-based analysis and RNA sequencing analysis, were performed to investigate the constituents of SCH and its molecular mechanisms in the suppression of TNBC. High-performance liquid chromatography and thin-layer chromatography were used to identify two major components, quercetin and β-sitosterol. Then, we discovered the synergistic cytotoxicity of quercetin and β-sitosterol and assessed their synergistic prevention of cell migration and invasion. Breast cancer xenografts were also created using MDA-MB-231 cells to test the synergistic therapeutic impact of quercetin and β-sitosterol on TNBC in vivo. The impact on the DNA damage and repair pathways was investigated using the comet assay and Western blot analysis. Our findings showed that SCH decreased TNBC cell growth, migration, and invasion while also inducing cell death. We identified quercetin and β-sitosterol as the core active components of SCH based on a network pharmacology study. According to RNA sequencing research, the p53 signaling pathway is also regarded as a critical biological mechanism of SCH treatment. The comet assay consistently showed that SCH significantly increased DNA damage in TNBC cells. Our in vivo and in vitro data revealed that the combination of quercetin and β-sitosterol induced synergistic cytotoxicity and DNA damage in TNBC cells. In particular, SCH particularly blocked the inter-strand cross-link repair mechanism and the double-strand breach repair caused by the homologous recombination pathway, in addition to inducing DNA damage. Treatment with quercetin and β-sitosterol produced similar outcomes. The current study provides novel insight into the previously unknown therapeutic potential of SCH as a DNA-damaging agent in TNBC.
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影响因子：
4.8
作者：
Debnath, J;Muthuswamy, SK;Brugge, JS
通讯作者：
Brugge, JS
DOI：
10.1080/01635581.2015.1087042
发表时间：
2015-11-17
影响因子：
2.9
作者：
Bin Sayeed, Muhammad Shahdaat;Ameen, Syeda Sadia
通讯作者：
Ameen, Syeda Sadia
影响因子：
5.4
作者：
Shu, Guangwen;Zhao, Wenhao;Xiang, Meixian
通讯作者：
Xiang, Meixian
影响因子：
11.2
作者：
Cheng H;Liu P;Zhang F;Xu E;Symonds L;Ohlson CE;Bronson RT;Maira SM;Di Tomaso E;Li J;Myers AP;Cantley LC;Mills GB;Zhao JJ
通讯作者：
Zhao JJ
影响因子：
45.3
作者：
Gourley, Charlie;Balmana, Judith;Boulton, Simon J.
通讯作者：
Boulton, Simon J.