Dandelion extract inhibits triple-negative breast cancer cell proliferation by interfering with glycerophospholipids and unsaturated fatty acids metabolism.
Dandelion extract inhibits triple-negative breast cancer cell proliferation by interfering with glycerophospholipids and unsaturated fatty acids metabolism.
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蒲公英提取物通过干扰甘油磷脂和不饱和脂肪酸代谢抑制三阴性乳腺癌细胞增殖
DOI：
10.3389/fphar.2022.942996
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发表时间：
2022
影响因子：
5.6
通讯作者：
Han, Shu-yan
中科院分区：
文献类型：
--
作者：
Wang, Shan;Hao, Hui-feng;Jiao, Yan-na;Fu, Jia-lei;Guo, Zheng-wang;Guo, Yang;Yuan, Yuan;Li, Ping-ping;Han, Shu-yan
关键词：
三阴性乳腺癌（TNBC）是最具侵袭性的乳腺癌亚型，治疗选择有限，预后较差。TNBC存在广泛的重编程脂质代谢，其代谢相关蛋白和肿瘤代谢物有望成为潜在的治疗靶点。蒲公英（Taraxacum mongolicum）是一种基于中医理论治疗乳腺疾病的经典草药，据报道具有抗肿瘤作用和调节脂质能力。我们之前的研究表明蒲公英提取物对TNBC有效。然而，蒲公英提取物是否通过干扰脂质代谢来调节TNBC的脂质代谢并发挥其抗肿瘤作用尚不清楚。本研究采用网络药理学和多组学技术（包括蛋白质组学、代谢组学和脂质组学）相结合的综合方法，研究蒲公英提取物对TNBC的潜在调控机制。我们首先测定了蒲公英提取物在体内和体外的抗肿瘤作用。网络药理学分析推测蒲公英提取物的抗肿瘤作用涉及多种代谢过程，细胞、肿瘤组织和血浆的多组学结果揭示了蒲公英提取物处理后代谢物和代谢相关蛋白的变化。代谢产物中甘油磷脂和不饱和脂肪酸的变化最为显著。因此，甘油磷脂和不饱和脂肪酸的代谢及其相应的蛋白CHKA和FADS2被认为是蒲公英提取物抗TNBC的主要调控途径和生物标志物。随后，实验验证表明，蒲公英提取物可降低CHKA的表达，从而抑制PI3K/AKT通路及其下游靶点SREBP和FADS2。最后，分子对接模拟显示蒲公英提取物中的苦味素苷F和木犀草素与CHKA结合得分最高，提示它们可能是调节TNBC甘油磷脂代谢的潜在CHKA抑制剂。综上所述，我们在体外实验中证实了蒲公英提取物对TNBC细胞的抗肿瘤作用，并证明蒲公英提取物可能通过下调CHKA表达和抑制PI3K/AKT/SREBP/FADS2轴来干扰甘油磷脂和不饱和脂肪酸代谢。
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype with limited treatment options and a poor prognosis. TNBC exists widely reprogrammed lipid metabolism, and its metabolic-associated proteins and oncometabolites are promising as potential therapeutic targets. Dandelion (Taraxacum mongolicum) is a classical herbal medicine used to treat breast diseases based on traditional Chinese medicine theory and was reported to have antitumor effects and lipid regulatory capacities. Our previous study showed that dandelion extract was effective against TNBC. However, whether dandelion extract could regulate the lipid metabolisms of TNBC and exert its antitumor effects via interfering with lipids metabolism remained unclear. In this study, an integrated approach combined with network pharmacology and multi-omics techniques (including proteomics, metabolomics, and lipidomics) was performed to investigate the potential regulatory mechanisms of dandelion extract against TNBC. We first determined the antitumor effects of dandelion extract in vitro and in vivo. Then, network pharmacology analysis speculated the antitumor effects involving various metabolic processes, and the multi-omics results of the cells, tumor tissues, and plasma revealed the changes in the metabolites and metabolic-associated proteins after dandelion extract treatment. The alteration of glycerophospholipids and unsaturated fatty acids were the most remarkable types of metabolites. Therefore, the metabolism of glycerophospholipids and unsaturated fatty acids, and their corresponding proteins CHKA and FADS2, were considered the primary regulatory pathways and biomarkers of dandelion extract against TNBC. Subsequently, experimental validation showed that dandelion extract decreased CHKA expression, leading to the inhibition of the PI3K/AKT pathway and its downstream targets, SREBP and FADS2. Finally, the molecular docking simulation suggested that picrasinoside F and luteolin in dandelion extract had the most highly binding scores with CHKA, indicating they may be the potential CHKA inhibitors to regulate glycerophospholipids metabolisms of TNBC. In conclusion, we confirmed the antitumor effects of dandelion extract against TNBC cells in vitro and demonstrated that dandelion extract could interfere with glycerophospholipids and unsaturated fatty acids metabolism via downregulating the CHKA expression and inhibiting PI3K/AKT/SREBP/FADS2 axis.
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影响因子：
5.7
作者：
Li X;Nakayama K;Goto T;Kimura H;Akamatsu S;Hayashi Y;Fujita K;Kobayashi T;Shimizu K;Nonomura N;Ogawa O;Inoue T
通讯作者：
Inoue T
影响因子：
4.1
作者：
Haukaas TH;Euceda LR;Giskeødegård GF;Bathen TF
通讯作者：
Bathen TF
影响因子：
5.4
作者：
Li, Xiao-Hong;He, Xi-Ran;Han, Shu-Yan
通讯作者：
Han, Shu-Yan
针对癌症中的磷脂代谢。
影响因子：
4.7
作者：
Cheng M;Bhujwalla ZM;Glunde K
通讯作者：
Glunde K
影响因子：
4.3
作者：
Davaatseren, Munkhtugs;Hur, Haeng Jeon;Sung, Mi Jeong
通讯作者：
Sung, Mi Jeong