Integrating UPLC-HR-MS/MS, Network Pharmacology, and Experimental Validation to Uncover the Mechanisms of Jin'gan Capsules against Breast Cancer
文献类型:期刊论文
作者 | Qiu, Jianfei2,3,4,5; Zhang, Zhiyin1; Hu, Anling2,3,4,5; Zhao, Peng2,3,4,5; Wei, Xuenai2,3,4,5; Song, Hui2,3,4,5; Yang, Jue2,3,4,5,6,7; Li, Yanmei2,3,4,5,6,7 |
刊名 | ACS OMEGA |
出版日期 | 2022-08-07 |
页码 | 13 |
ISSN号 | 2470-1343 |
DOI | 10.1021/acsomega.2c01921 |
通讯作者 | Song, Hui(songhui620@126.com) ; Yang, Jue(yaodadewo@163.com) ; Li, Yanmei(liyanmei518@hotmail.com) |
英文摘要 | In the theory of traditional Chinese medicine (TCM), "liver-qi " stagnation and heat-induced toxicity represent the main etiologies of breast cancer. Recently, several TCMs with heat-clearing and detoxification efficacy have shown inhibitory effects on breast cancer. Jin'gan capsules (JGCs), initially approved to treat colds in China, are a heat-clearing and detoxification TCM formula. However, the anticancer activity of JGCs against breast cancer and its underlying mechanisms remain unclear. First, we assessed the antiproliferative activity of JGCs in breast cancer cell lines and evaluated their effects on cell apoptosis and the cell cycle by flow cytometry. Furthermore, we identified the potential bioactive components of JGCs and their corresponding target genes and constructed a bioactive compound-target interaction network by ultra-performance liquid chromatography-high-resolution tandem mass spectrometry (UPLC-HR-MS/MS) and network pharmacology analysis. Finally, the underlying mechanism was investigated through gene function enrichment analysis and experimental validation. We found that JGCs significantly inhibited breast cancer cell growth with IC50 values of 0.56 +/- 0.03, 0.16 +/- 0.03, and 0.94 +/- 0.09 mg/mL for MDA-MB-231, MDA-MB-468, and MCF-7, respectively. In addition, JGC treatment dramatically induced apoptosis and S phase cell cycle arrest in breast cancer cells. Western blot analysis confirmed that JGCs could regulate the protein levels of apoptosis-and cell cycle-related genes. Utilizing UPLC-HR-MS/MS analysis and network pharmacology, we identified 7 potential bioactive ingredients in JGCs and 116 antibreast cancer targets. Functional enrichment analysis indicated that the antitumor effects of JGCs were strongly associated with apoptosis and the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. Western blot analysis validated that JGC treatment markedly decreased the expression levels of p-JAK2, p-STAT3, and STAT3. Our findings suggest that JGCs suppress breast cancer cell proliferation and induce cell cycle arrest and apoptosis partly by inhibiting the JAK2/STAT3 signaling pathway, highlighting JGCs as a potential therapeutic candidate against breast cancer. |
WOS关键词 | NF-KAPPA-B ; CELL-MIGRATION ; INVASION ; PATHWAY ; NEOANDROGRAPHOLIDE ; ANDROGRAPHOLIDE ; EXPRESSION ; PREDICTION ; APOPTOSIS ; PUERARIN |
资助项目 | National Natural Science Foundation of China ; State Key Laboratory of Drug Research ; Science and Technology Department of Guizhou Province ; 100 Leading Talents of Guizhou Province ; Guizhou Provincial Science and Technology Projects ; Project of Key Laboratory of Endemic and Ethnic Diseases, Ministry of Education, Guizhou ; [82160813] ; [32060210] ; [81872772] ; [81960546] ; [U1812403] ; [SIMM2105KF-15] ; [[2 0 1 8] 1409] ; [[2 0 1 9] 2 7 6 2] ; [[2020] 5008] ; [4Y203] ; [P2018-KF11] ; [QZYY-2019-022] ; [QKHZK [2021] 526] ; [[2021] 448] |
WOS研究方向 | Chemistry |
语种 | 英语 |
出版者 | AMER CHEMICAL SOC |
WOS记录号 | WOS:000844597000001 |
源URL | [http://119.78.100.183/handle/2S10ELR8/302317] |
专题 | 新药研究国家重点实验室 |
通讯作者 | Song, Hui; Yang, Jue; Li, Yanmei |
作者单位 | 1.Guiyang Hosp, Guizhou Aviat Ind Grp, Guiyang 550025, Peoples R China 2.Guizhou Med Univ, Key Lab Med Mol Biol Guizhou Prov, Guiyang 550004, Peoples R China 3.Guizhou Med Univ, Key Lab Endem & Ethn Dis, Minist Educ, Guiyang 550004, Peoples R China 4.Chinese Acad Sci, Guiyang 550004, Peoples R China 5.Guizhou Med Univ, Key Lab Chem Nat Prod Guizhou Prov, Guiyang 550004, Peoples R China 6.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China 7.Guizhou Med Univ, State Key Lab Funct & Applicat Med Plants, Guiyang 550014, Peoples R China |
推荐引用方式 GB/T 7714 | Qiu, Jianfei,Zhang, Zhiyin,Hu, Anling,et al. Integrating UPLC-HR-MS/MS, Network Pharmacology, and Experimental Validation to Uncover the Mechanisms of Jin'gan Capsules against Breast Cancer[J]. ACS OMEGA,2022:13. |
APA | Qiu, Jianfei.,Zhang, Zhiyin.,Hu, Anling.,Zhao, Peng.,Wei, Xuenai.,...&Li, Yanmei.(2022).Integrating UPLC-HR-MS/MS, Network Pharmacology, and Experimental Validation to Uncover the Mechanisms of Jin'gan Capsules against Breast Cancer.ACS OMEGA,13. |
MLA | Qiu, Jianfei,et al."Integrating UPLC-HR-MS/MS, Network Pharmacology, and Experimental Validation to Uncover the Mechanisms of Jin'gan Capsules against Breast Cancer".ACS OMEGA (2022):13. |
入库方式: OAI收割
来源:上海药物研究所
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