Wogonoside prevents colitis-associated colorectal carcinogenesis and colon cancer progression in inflammation-related microenvironment via inhibiting NF-κB activation through PI3K/Akt pathway.
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.
State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.|Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.|Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
Yang
Y
Sun
State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.|Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.|Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
Yue
Y
Zhao
State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.|Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.|Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
Xiaoping
X
Wang
State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.|Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.|Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
Li
L
Zhao
State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.|Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.|Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
Wenjun
W
Li
State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.|Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.|Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
Youxiang
Y
Ding
State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.
Lingyi
L
Kong
State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.|Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.|Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
Qinglong
Q
Guo
State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, Nanjing 210009, China.|Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Nanjing 210009, China.|Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China.
Na
N
Lu
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D063646:Carcinogenesis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003092:Colitis / Q000150:complications; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D044950:Flavanones / Q000494:pharmacology*; D005960:Glucosides / Q000494:pharmacology*; D006801:Humans; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D059016:Tumor Microenvironment / Q000187:drug effects
D000970:Antineoplastic Agents; D044950:Flavanones; D005960:Glucosides; D016328:NF-kappa B; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C473995:wogonoside
AOM/DSS mouse model; NF-κB; colitis-associated cancer; wogonoside