Anti-inflammatory activities of natural cyclopeptide RA-XII in colitis-associated colon cancer mouse model and its effect on gut microbiome.
Qianwen LinMingyu LiuGrace Gar-Lee YueMan Kit CheungZhixing LaiFrankie Hin-Fai KwokJulia Kin-Ming LeeZhe WangClara Bik San LauNing-Hua TanPublished in: Phytotherapy research : PTR (2022)
Colorectal cancer (CRC), the third most common cancer globally, is associated with intestinal inflammation that leads to poor prognosis. RA-XII, a natural cyclopeptide, has previously been reported to possess anti-tumor activities. Here, the anti-inflammatory activities of RA-XII were investigated in colitis-associated colon cancer mice and a co-culture in vitro model, in which colon cancer cells HCT116 and macrophages RAW264.7 were grown together to mimic the inflammatory microenvironment of CRC. Changes of inflammatory-related molecules and protein expressions in cells were evaluated after RA-XII incubation. Besides, azoxymethane and dextran sulfate sodium-induced colitis-associated colon cancer mice were treated with RA-XII for 24 days, inflammatory parameters and gut microbiome alterations were studied. Our results showed that RA-XII reversed the inflammatory responses of RAW264.7 cells induced by LPS and modulated the protein expressions of AKT, STAT3/p-STAT3, P70S6K, NF-κB and GSK3β and suppressed the expression of LC3A/B in HCT116 cells in co-culture system. RA-XII treatment restored the colitis damage in colon, reduced colon tumors numbers and decreased inflammatory factors (IL-6, IL-10 and TNF-α). The role of RA-XII on regulating gut microbiome was also demonstrated for the first time. In conclusion, our findings provided new scientific evidence for developing RA-XII as a potent anti-inflammatory agent for CRC.
Keyphrases
- rheumatoid arthritis
- anti inflammatory
- poor prognosis
- disease activity
- oxidative stress
- induced apoptosis
- cell cycle arrest
- ankylosing spondylitis
- signaling pathway
- interstitial lung disease
- mouse model
- long non coding rna
- cell proliferation
- systemic lupus erythematosus
- cell death
- stem cells
- squamous cell carcinoma
- inflammatory response
- adipose tissue
- mass spectrometry
- newly diagnosed
- immune response
- nuclear factor
- idiopathic pulmonary fibrosis
- insulin resistance
- skeletal muscle
- smoking cessation
- solid phase extraction
- replacement therapy