Dandelion extract inhibits triple-negative breast cancer cell proliferation by interfering with glycerophospholipids and unsaturated fatty acids metabolism

Abstract

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.

Unraveling Biomarker Signatures in Triple-Negative Breast Cancer: A Systematic Review for Targeted Approaches

“…Specifically, BC is characterized by substantial metabolic heterogeneity. Therefore, targeting these metabolic alterations represents a promising therapeutic strategy [ 53 , 54 ].…”

“…A total of 60% of TNBC cases exhibit abnormal lipids metabolism pathways. This observation has raised significant interest in exploring metabolic-associated proteins and oncometabolites as promising therapeutic targets [ 54 ]. In a study targeting cancerous cells with dandelion extract, an herbal medicine with antitumor effects and lipid regulatory properties, changes in glycerophospholipids and unsaturated fatty acids emerged as the most prominent metabolite alterations in TNBC.…”

“…Additionally, dandelion extract reduced the expression of CHKA, resulting in PI3K/AKT pathway inhibition and its downstream targets, SREBP and FADS2. Notably, picrasinoside F and luteolin exhibited the highest binding scores with CHKA, suggesting their potential as inhibitors to regulate glycerophospholipids metabolism in TNBC [ 54 ].…”

Bibliometric and visual analysis in the field of traditional Chinese medicine in cancer from 2002 to 2022

“…In fact, many studies have confirmed the effectiveness of TCM in treating these five types of cancer and have elucidated their mechanisms of action. For instance, Wang et al (2022) reported that dandelion extract inhibited triple-negative breast cancer cell proliferation by interfering with glycerophospholipids and unsaturated fatty acid metabolism. Zhai et al (2022) found that red ginseng polysaccharides exhibited anti-ferroptosis effects in the lung and breast cancer cells by targeting GPX4.…”

Antiviral activity of dandelion aqueous extract against pseudorabies virus both in vitro and in vivo

“…Dandelion is a traditional medicinal and edible plant and has a history of thousands of years in China; it contains not only diverse bioactive components but also high dietary fiber and protein contents, as well as a large variety of amino acids and most minerals and vitamins ( 23 ). Therapeutically, dandelion has broad-spectrum antibacterial, antioxidant, diuretic, anti-inflammatory, and tumor apoptosis-inducing properties and can treat numerous diseases, such as acute inflammatory, neoplastic, urological, and diabetic syndromes ( 24 – 26 ). Additionally, the dandelion extract is a common antiviral agent used in TCM and has been reported to exhibit antiviral capabilities against HIV-1, influenza virus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and hepatitis B virus ( 27 – 30 ).…”