Effect of xanthohumol on Th1/Th2 balance in a breast cancer mouse model.

Abstract

Xanthohumol (XN), a prenylflavonoid found in the hop plant, Humulus lupulus, exhibits a variety of biological activities. Numerous studies have reported that XN inhibits the growth of many types of cancer cells, but the effects of XN on tumor immunity have not yet been studied. We explored the effect of XN on Th1/Th2 balance and the underlying mechanism based on a BALB/c-4T1 breast cancer mouse model. The results showed that XN significantly slowed down tumor growth and inhibited expression of antitumor proliferation protein Ki-67 as well as breast cancer-specific marker cancer antigen 15-3 (CA15-3). Flow cytometric analysis revealed that XN enhanced the secretion of perforin, granzyme B and increased the ratio of CD8+/CD25+. ELISA analysis of cytokine results demonstrated that XN obviously upregulated Th1 cytokines, while downregulated Th2 cytokines. Th1/Th2 ratio analysis by flow cytometry illustrated that XN regulated the balance drift to Th1 polarization. Western blotting and immunohistochemistry (IHC) results manifested that XN induced expression of T-bet, a Th1-specific transcription factor. Furthermore, we found that XN significantly promoted the phosphorylation of signal transducer and activator of transcription (STAT)4. Our results demonstrated that XN promoted Th1/Th2 balance towards Th1 polarization, and STAT4 may play a positive role in the regulation of Th1/Th2 cytokines by XN.

• Authors: Wenchao Zhang, Yanlong Pan, Panhong Gou, Cheng Zhou, Lianqing Ma, Qiming Liu, Yuping Du, Jinbo Yang, Qin Wang
• Journal: Oncology reports (Oncol Rep) Vol. 39 Issue 1 Pg. 280-288 (Jan 2018) ISSN: 1791-2431 [Electronic] Greece
• PMID: 29138867 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents, Phytogenic
• Flavonoids
• Ki-67 Antigen
• MUC1 protein, human
• Mucin-1
• Propiophenones
• Receptors, Notch
• xanthohumol

Topics

• Animals
• Antineoplastic Agents, Phytogenic (administration & dosage, pharmacology)
• Breast Neoplasms (drug therapy, immunology, metabolism)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cell Survival (drug effects)
• Female
• Flavonoids (administration & dosage, pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Humans
• Ki-67 Antigen (metabolism)
• Mice
• Mice, Inbred BALB C
• Mucin-1 (metabolism)
• Propiophenones (administration & dosage, pharmacology)
• Receptors, Notch (metabolism)
• Signal Transduction (drug effects)
• Th1 Cells (drug effects, immunology)
• Th2 Cells (drug effects, immunology)
• Xenograft Model Antitumor Assays