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.

Antiproliferative and Cytotoxic Activity of Xanthohumol and Its Non-Estrogenic Derivatives in Colon and Hepatocellular Carcinoma Cell Lines

“…They observed no changes in mouse body weight. Furthermore, administration of XN in xenograft models of breast, leukemia, prostate, pancreatic, gastric, and cholangiocarcinoma cells inhibits tumor growth [29,41,57,58,59,60,61,62,63]. Taken together, these data suggest that XN and its derivatives show promise in future studies.…”

Identification of immune cells and mRNA associated with prognosis of gastric cancer

“…Mast cells have the ability to facilitate tumor proliferation and invasion directly,and indirectly promote tumor proliferation and invasion by regulating tumor microenvironment [22], it may provide further evidence for Mast cells can be applied in the adjuvant treatment of mammary adenocarcinoma and melanoma [23]. Previous studies have shown that Th2 cells, T helper cells, and Mast cells may play key roles in the development and invasion of cancer [24][25][26][27], our studies show that these immune cells may play a role in gastric cancer.…”

Contribution to Tumor Angiogenesis From Innate Immune Cells Within the Tumor Microenvironment: Implications for Immunotherapy

“…CDDO-Im (a synthetic triterpenoid: 1[2-Cyano-3,12-dioxooleana-1,9(11)-dien-28-oyl]imidazole) has an extensive documentation as an immunomodulation agent ( 253 – 255 ), and xanthohumol (XN) (a prenylated chalcone flavonoid) is an antileukemia agent ( 256 – 259 ) and is a polarizing agent in murine models of breast cancer ( 260 ). Phytocompounds and their synthetic derivatives are able to polarize macrophages inducing anti-tumorigenic phenotype/functions ( 253 , 260 – 262 ). For example, we show that NSCLC patient TANKs treated with metformin, CDDO-Im, and XN decreases VEGF production (Figure 5 ) and increases perforin content.…”