Wogonoside prevents colitis-associated colorectal carcinogenesis and colon cancer progression in inflammation-related microenvironment via inhibiting NF-κB activation through PI3K/Akt pathway

Abstract

The inflammatory microenvironment has been reported to be correlated with tumor initiation and malignant development. In the previous studies we have found that wogonoside exerts anti-neoplastic and anti-inflammatory activities. In this study, we aimed to further investigate the chemopreventive effects of wogonoside on colitis-associated cancer and delineated the potential mechanisms. In the azoxymethane initiated and dextran sulfate sodium (AOM/DSS) promoted colorectal carcinogenesis mouse model, wogonoside significantly reduced the disease severity, lowered tumor incidence and inhibited the development of colorectal adenomas. Moreover, wogonoside inhibited inflammatory cells infiltration and cancer cell proliferation at tumor site. Furthermore, wogonoside dramatically decreased the secretion and expression of IL-1β, IL-6 and TNF-α as well as the nuclear expression of NF-κB in adenomas and surrounding tissues. In vitro results showed that wogonoside suppressed the proliferation of human colon cancer cells in the inflammatory microenvironment. Mechanistically, we found that wogonoside inhibited NF-κB activation via PI3K/Akt pathway. In conclusion, our results demonstrated that wogonoside attenuated colitis-associated tumorigenesis in mice and inhibited the progression of human colon cancer in inflammation-related microenvironment via suppressing NF-κB activation by PI3K/Akt pathway, indicating that wogonoside could be a promising therapeutic agent for colorectal cancer.

Wogonoside inhibits cell growth and induces mitochondrial-mediated autophagy-related apoptosis in human colon cancer cells through the PI3K/AKT/mTOR/p70S6K signaling pathway

“…In the present study, wogonoside was observed to significantly suppress PI3K and p-AKT protein expression in LOVO cells. Sun et al (25) suggested that wogonoside prevents colitis-associated colorectal carcinogenesis through inhibiting nuclear transcription facto-κB (NF-κB) activation via the PI3K/Akt signaling pathway.…”

Targeting NF-κB pathway for treating ulcerative colitis: comprehensive regulatory characteristics of Chinese medicines

“…In addition, evidence indicates that wogonin (25 mg/mL) treatment obviously attenuates the inflammatory response of toll like receptor (TLR4)-myeloid differentiation factor (MyD) 88-mediated NF-κB pathway in lipopolysaccharide (LPS)-induced intestinal inflammation of Caco-2 cells in vitro, suggesting protective function on intestinal mucosal barrier [47]. As for wogonoside (12.5, 25 or 50 mg/kg), its application inhibits the activation of NF-κB-induced NLRP3 inflammasomes in DSS-induced colitis and colitis-associated tumorigenesis in mice [48,49].…”

“…Inhibit the protein expression of p-p65 [49] THP-1 cells Suppress NF-κB nuclear translocation [49] Berberine Colonic macrophages and epithelial cells…”

High‐dose wogonin exacerbates DSS‐induced colitis by up‐regulating effector T cell function and inhibiting Treg cell

“…Wogonoside, as the glucuronide metabolite of wogonin, at dosages of 12.5, 25 or 50 mg/kg intragastrically, protects against DSS-induced experimental colitis in mice by inhibiting NF-jB and NLRP3 inflammasome activation [35]. Firstly, whether the effect of wogonoside is different from that of wogonin need further study.…”