Wogonin Inhibits Tumor-derived Regulatory Molecules by Suppressing STAT3 Signaling to Promote Tumor Immunity.

Abstract

Wogonin exerts effective antitumor activities through direct cytotoxicity against cancer cells and indirect immune modulation. However, the molecular mechanisms of these activities remain poorly understood and need further study. We found that wogonin could efficiently downregulate the expression of B7H1, retinoic acid early induced transcript-1ε (RAE-1ε), and vascular endothelial growth factor in gastric cancer cells. Wogonin also promoted the secretion of calreticulin and high-mobility group protein 1 by tumor cells. Apoptotic bodies from dying tumor cells treated with wogonin were susceptible for uptake by neighboring dendritic cells (DCs). With the xenograft tumor model, wogonin inhibited tumor growth and promoted the recruitment of DC, T, and NK cells into tumor tissues. Infiltrated frequencies of DC, T, and NK cells in tumors were inversely correlated with expression levels of vascular endothelial growth factor, B7H1, and RAE-1ε of tumor tissues. Wogonin directly inhibited the activation of STAT3 on tyrosine 705 in tumor cells. The dephosphorylation of STAT3 contributed to the decreased expression of B7H1 and MHC class I chain-related protein A, and the enhancement of calreticulin on the cell membrane. Our study confirmed the immune-enhancing function of wogonin, and indicated that wogonin could be used in collaboration with DC vaccine or activated lymphocytes for tumor therapy.

• Authors: Weiming Xiao, Keyan Wu, Min Yin, Sen Han, Yanbing Ding, Ahui Qiao, Guotao Lu, Bing Deng, Ping Bo, Weijuan Gong
• Journal: Journal of immunotherapy (Hagerstown, Md. : 1997) (J Immunother) Vol. 38 Issue 5 Pg. 167-84 (Jun 2015) ISSN: 1537-4513 [Electronic] United States
• PMID: 25962106 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents, Phytogenic
• B7-H1 Antigen
• Flavanones
• Histocompatibility Antigens Class I
• MHC class I-related chain A
• STAT3 Transcription Factor
• Vascular Endothelial Growth Factor A
• wogonin

Topics

• Animals
• Antineoplastic Agents, Phytogenic (pharmacology)
• Apoptosis (drug effects)
• B7-H1 Antigen (genetics, metabolism)
• Cell Line, Tumor
• Dendritic Cells (drug effects, immunology, metabolism)
• Disease Models, Animal
• Down-Regulation
• Flavanones (pharmacology)
• Histocompatibility Antigens Class I (genetics, metabolism)
• Humans
• Immunomodulation (drug effects)
• Lymphocytes, Tumor-Infiltrating (immunology, metabolism)
• Mice
• Neoplasms (drug therapy, genetics, immunology, metabolism, mortality, pathology)
• Phagocytosis (drug effects)
• Phosphorylation
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects)
• T-Lymphocyte Subsets (immunology, metabolism, pathology)
• Vascular Endothelial Growth Factor A (genetics, metabolism)
• Xenograft Model Antitumor Assays