Abstract
Altered gut microbiota and a damaged colon mucosal barrier have been implicated in the development of colon cancer. Astragalus mongholicus Bunge-Curcuma aromatica Salisb. (ACE) is a common herbal drug pair that widely used clinically to treat cancer. However, whether the anti-cancer effect of ACE is related to gut microbiota remains unclear yet. We standardized ACE and investigated the effects of ACE on tumour suppression and analyze the related mechanisms on gut microbiota in CT26 colon cancer-bearing mice in the present study. Firstly, four flavonoids (calycosin-7-glucoside, ononin, calycosin, formononetin) and three astragalosides (astragaloside A, astragaloside II, astragaloside I) riched in Astragalus mongholicus Bunge, three curcumins (bisdemethoxycurcumin, demethoxycurcumin, curcumin) and four essential oils (curdione, curzerene, germacrone and β-elemene) from Curcuma aromatica Salisb., in concentrations from 0.08 to 2.07 mg/g, were examined in ACE. Then the results in vivo studies indicated that ACE inhibited solid tumours, liver and spleen metastases of colon cancer while simultaneously reducing pathological tissue damage. Additionally, ACE regulated gut microbiota dysbiosis and the short chain fatty acid content in the gut, repaired intestinal barrier damage. ACE treatment suppressed the overgrowth of conditional pathogenic gut bacteria, including Escherichia-Shigella, Streptococcus and Enterococcus, while the probiotic gut microbiota like Lactobacillus, Roseburia, Prevotellaceae_UCG-001 and Mucispirillum were increased. More interestingly, the content level of SCFAs such as propionic acid and butyric acid was increased after ACE administration, which further mediates intestinal SDF-1/CXCR4 signalling pathway to repair the integrity of the intestinal barrier, decrease Cyclin D1 and C-myc expressions, eventually suppress the tumor the growth and metastasis of colon cancer. To sum up, the present study demonstrated that ACE could efficiently suppress colon cancer progression through gut microbiota modification, which may provide a new explanation of the mechanism of ACE against colon cancer.
Highlights
Colorectal cancer (CRC) is reported to be a leading cause of death worldwide, the mean age at diagnosis is getting younger, and the incidence of colon cancer is higher than that of rectal cancer (Siegel et al, 2020)
Body weight after tumour removal and thymus indices of the mice in the model and 5-FU groups were significantly lower than the sham mice (p < 0.01), while the mice in the aromatica Salisb. [Zingiberaceae; Curcumae Rhizoma] (ACE) group had significantly higher body weight and enhanced immune function compared with tumour-bearing mice in model group (p < 0.01, Figures 2B,C)
These results demonstrated that ACE could improve the body weight of tumour-bearing mice and inhibit the growth of colon cancer to a certain degree
Summary
Colorectal cancer (CRC) is reported to be a leading cause of death worldwide, the mean age at diagnosis is getting younger, and the incidence of colon cancer is higher than that of rectal cancer (Siegel et al, 2020). Local recurrence and distal metastasis rates after surgical resection contribute to the lethal nature of CRC (Backes et al, 2019). It is not surprising that the intestinal microbiome, the barrier that mediates between our environment and our genes, has been seen as a main cause of many diseases, such as colon cancer, diabetes, obesity, and the development of autoimmune diseases (Imhann et al, 2018; Sethi et al, 2018; Olsson et al, 2020). Symbiotic bacteria can directly contribute to the development of colon cancer by increasing gene mutations in epithelial cells or activating specific oncogenic pathways, while the flora can strongly regulate the host’s immune system to influence tumour growth indirectly (Cremonesi et al, 2018). Single species with oncogenes have been identified as a result of developments in biological technology, including BFT toxin expressed by enterotoxigenic Bacteroides fragilis (ETBF), pks virulence islands by Escherichia coli, and the FadA and Fap adhesins by Fusobacterium nucleatum (Arthur et al, 2012; Bullman et al, 2017)
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