ReferenceID 4629
Baicalein Potentiated M1 Macrophage Polarization in Cancer Through Targeting PI3Kγ/ NF-κB Signaling
Front Pharmacol
Baicalein is one of the bioactive compounds extracted from Scutellaria baicalensis. Recent studies indicated the antitumor effects of baicalein, however, the underlying mechanisms are needed to be further determined. In
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 4629
- Evidence Id
- 21219
- Core Evidence Id
- 21219
- Source Reference Id
- 2525
- Herb2 Reference Id
- HBREF003322
- Subject Paper Key
- HBIN017508_34512367
- Pubmed Id
- 34512367
- Doi
- 10.3389/fphar.2021.743837
- Paper Title
- Baicalein Potentiated M1 Macrophage Polarization in Cancer Through Targeting PI3Kγ/ NF-κB Signaling
- Paper Abstract
- Baicalein is one of the bioactive compounds extracted from Scutellaria baicalensis. Recent studies indicated the antitumor effects of baicalein, however, the underlying mechanisms are needed to be further determined. In this study, we found that baicalein could inhibit the tumor growth in mice models of breast cancer and melanoma and worked as an immunomodulator to promote the infiltration of tumor-associated macrophages (TAMs) and skew the TAMs towards the M1-like phenotype. Baicalein also induced M1-like phenotype polarization in THP-1-derived macrophages. Meanwhile, the expression of pro-inflammatory factors associated with M1 macrophages, including TNF-alpha, IL-1beta, CXCL9 and CXCL10, were increased after baicalein treatment. Mechanistically, the RNA-seq data suggested that baicalein potentiated the M1 macrophage polarization via the NF-kappaB/TNF-alpha signaling pathway. ELISA and confocal microscopy assay confirmed that baicalein significantly induced the production of TNF-alpha and the activation of NF-kappaB, while TNF-alpha neutralization inhibited baicalein-induced macrophage polarization toward M1, and NF-kappaB P65 knock-down suppressed baicalein-induced TNF-alpha production in THP-1-derived macrophages. Phosphoinositide 3-kinase (PI3k) gamma has been reported as a key molecule in macrophage polarization, and inhibition of PI3Kgamma activates the NF-kappaB-related inflammatory signals. Our pharmacological network analysis predicted that PI3Kgamma might be one of the major targets of baicalein. The results from the docking program and surface plasmon resonance (SPR) confirmed that baicalein displayed good binding activity to PI3Kgamma. We further found that baicalein not only exhibited a direct inhibitory effect on the protein kinase activity of PI3Kgamma, but also reduced the mRNA and protein expression of PI3Kgamma, indicating that baicalein might be a novel PI3Kgamma inhibitor. In summary, baicalein mediated the TAMs skewing to M1-TAMs, and then retarded tumor growth. These effects, at least in part, were linked to the PI3Kgamma/NF-kappaB signaling.
- Journal
- Front Pharmacol
- Publish Year
- 2021
- Experiment Subject
- mouse; thp-1-derived macrophages
- Experiment Type
- Clinical Experiment
- Phenotype Related
- Melanoma; Tumor; Breast Cancer
- Paper Title Cn
- Paper Title En
- Baicalein Potentiated M1 Macrophage Polarization in Cancer Through Targeting PI3Kγ/ NF-κB Signaling
- Bilingual Status
- semi_complete