Generic placeholder image

Anti-Cancer Agents in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1871-5206
ISSN (Online): 1875-5992

Research Article

Ginsenoside Rb1 Suppresses AOM/DSS-induced Colon Carcinogenesis

Author(s): Ling Wang, Qing-Qing Zhang, Yu-Yu Xu, Rui Zhang, Qing Zhao, Yu-Qing Zhang, Xue-Hong Huang, Bin Jiang* and Min Ni*

Volume 23, Issue 9, 2023

Published on: 20 February, 2023

Page: [1067 - 1073] Pages: 7

DOI: 10.2174/1871520623666230119092735

Price: $65

Abstract

Background: Colorectal cancer (CRC) is the third most common cancer worldwide. Current treatments, including surgery, radiotherapy, and chemotherapy, are limited by severe side effects and the development of resistance.

Objective: Therefore, it is important to find additional therapies to combat the problem. Ginsenoside Rb1 is the main active ingredient of ginseng, which is a well-known herb in traditional Chinese medicine. Ginsenoside is reported to play an important role in the prevention and treatment of cancer.

Methods: We established Azoxymethane (AOM)/Dextran sodium sulfate (DSS) colon cancer model based on inflammation, observed the beneficial effect of ginsenoside Rb1, and detected the changes in gut microbiota.

Results: Our experimental results showed that ginsenoside Rb1 significantly reduced the levels of TNF-α, IL-6, IL- 17A, IL-33, IL-1β, and IL-22, increased the level of IL-10, and also changed the gut microbiota composition. These results suggested that ginsenoside Rb1 can be used to prevent inflammation-associated CRC development and may provide an effective therapeutic strategy for CRC by relieving chronic inflammation and restoring the gut microenvironment in the AOM/DSS-induced model of colitis-associated colorectal cancer in mice.

Conclusion: Ginsenoside Rb1 significantly attenuated AOM/DSS-induced colon carcinogenesis.

Keywords: Colorectal cancer, ginsenoside Rb1, inflammation, gut microenvironment, colitis, carcinogenesis.

Graphical Abstract
[1]
Torre, L.A.; Bray, F.; Siegel, R.L.; Ferlay, J.; Lortet-Tieulent, J.; Jemal, A. Global cancer statistics, 2012. CA Cancer J. Clin., 2015, 65(2), 87-108.
[http://dx.doi.org/10.3322/caac.21262] [PMID: 25651787]
[2]
Edwards, B.K.; Ward, E.; Kohler, B.A.; Eheman, C.; Zauber, A.G.; Anderson, R.N.; Jemal, A.; Schymura, M.J.; Lansdorp-Vogelaar, I.; Seeff, L.C.; van Ballegooijen, M.; Goede, S.L.; Ries, L.A.G. Annual report to the nation on the status of cancer, 1975-2006, featuring colorectal cancer trends and impact of interventions (risk factors, screening, and treatment) to reduce future rates. Cancer, 2010, 116(3), 544-573.
[http://dx.doi.org/10.1002/cncr.24760] [PMID: 19998273]
[3]
Farraye, F.A.; Odze, R.D.; Eaden, J.; Itzkowitz, S.H.; McCabe, R.P.; Dassopoulos, T.; Lewis, J.D.; Ullman, T.A.; James, T., III; McLeod, R.; Burgart, L.J.; Allen, J.; Brill, J.V. AGA medical position statement on the diagnosis and management of colorectal neoplasia in inflammatory bowel disease. Gastroenterology, 2010, 138(2), 738-745.
[http://dx.doi.org/10.1053/j.gastro.2009.12.037] [PMID: 20141808]
[4]
Lucas, C.; Barnich, N.; Nguyen, H. Microbiota, inflammation and colorectal cancer. Int. J. Mol. Sci., 2017, 18(6), 1310.
[http://dx.doi.org/10.3390/ijms18061310] [PMID: 28632155]
[5]
Ahuja, A.; Kim, J.H.; Kim, J.H.; Yi, Y.S.; Cho, J.Y. Functional role of ginseng-derived compounds in cancer. J. Ginseng Res., 2018, 42(3), 248-254.
[http://dx.doi.org/10.1016/j.jgr.2017.04.009] [PMID: 29983605]
[6]
Yao, H.; Wan, J.Y.; Zeng, J.; Huang, W.H.; Sava-Segal, C.; Li, L.; Niu, X.; Wang, Q.; Wang, C.Z.; Yuan, C.S. Effects of compound K, an enteric microbiome metabolite of ginseng, in the treatment of inflammation associated colon cancer. Oncol. Lett., 2018, 15(6), 8339-8348.
[http://dx.doi.org/10.3892/ol.2018.8414] [PMID: 29805567]
[7]
Huang, G.; Khan, I.; Li, X.; Chen, L.; Leong, W.; Ho, L.T.; Hsiao, W.L.W. Ginsenosides Rb3 and Rd reduce polyps formation while reinstate the dysbiotic gut microbiota and the intestinal microenvironment in ApcMin/+ mice. Sci. Rep., 2017, 7(1), 12552.
[http://dx.doi.org/10.1038/s41598-017-12644-5] [PMID: 28970547]
[8]
Yu, L.C.H.; Wei, S.C.; Ni, Y.H. Impact of microbiota in colorectal carcinogenesis: Lessons from experimental models. Intest. Res., 2018, 16(3), 346-357.
[http://dx.doi.org/10.5217/ir.2018.16.3.346] [PMID: 30090033]
[9]
Leystra, A.A.; Clapper, M.L. Gut microbiota influences experimental outcomes in mouse models of colorectal cancer. Genes, 2019, 10(11), 900.
[http://dx.doi.org/10.3390/genes10110900] [PMID: 31703321]
[10]
Wu, M.; Li, J.; An, Y.; Li, P.; Xiong, W.; Li, J.; Yan, D.; Wang, M.; Zhong, G. Chitooligosaccharides prevents the development of colitis-associated colorectal cancer by modulating the intestinal microbiota and mycobiota. Front. Microbiol., 2019, 10, 2101.
[http://dx.doi.org/10.3389/fmicb.2019.02101] [PMID: 31620100]
[11]
Man, S.M.; Zhu, Q.; Zhu, L.; Liu, Z.; Karki, R.; Malik, A.; Sharma, D.; Li, L.; Malireddi, R.K.S.; Gurung, P.; Neale, G.; Olsen, S.R.; Carter, R.A.; McGoldrick, D.J.; Wu, G.; Finkelstein, D.; Vogel, P.; Gilbertson, R.J.; Kanneganti, T.D. Critical role for the DNA sensor AIM2 in stem cell proliferation and cancer. Cell, 2015, 162(1), 45-58.
[http://dx.doi.org/10.1016/j.cell.2015.06.001] [PMID: 26095253]
[12]
Guo, M.; Wang, H.; Xu, S.; Zhuang, Y.; An, J.; Su, C.; Xia, Y.; Chen, J.; Xu, Z.Z.; Liu, Q.; Wang, J.; Dan, Z.; Chen, K.; Luan, X.; Liu, Z.; Liu, K.; Zhang, F.; Xia, Y.; Liu, X. Alteration in gut microbiota is associated with dysregulation of cytokines and glucocorticoid therapy in systemic lupus erythematosus. Gut Microbes, 2020, 11(6), 1758-1773.
[http://dx.doi.org/10.1080/19490976.2020.1768644] [PMID: 32507008]
[13]
Wang, C.Z.; Yu, C.; Wen, X.D.; Chen, L.; Zhang, C.F.; Calway, T.; Qiu, Y.; Wang, Y.; Zhang, Z.; Anderson, S.; Wang, Y.; Jia, W.; Yuan, C.S. American ginseng attenuates colitis-associated colon carcinogenesis in mice: Impact on gut microbiota and metabolomics. Cancer Prev. Res., 2016, 9(10), 803-811.
[http://dx.doi.org/10.1158/1940-6207.CAPR-15-0372] [PMID: 27443884]
[14]
Loke, Y.L.; Chew, M.T.; Ngeow, Y.F.; Lim, W.W.D.; Peh, S.C. Colon carcinogenesis: The interplay between diet and gut microbiota. Front. Cell. Infect. Microbiol., 2020, 10, 603086.
[http://dx.doi.org/10.3389/fcimb.2020.603086] [PMID: 33364203]
[15]
Chen, H.M.; Yu, Y.N.; Wang, J.L.; Lin, Y.W.; Kong, X.; Yang, C.Q.; Yang, L.; Liu, Z.J.; Yuan, Y.Z.; Liu, F.; Wu, J.X.; Zhong, L.; Fang, D.C.; Zou, W.; Fang, J.Y. Decreased dietary fiber intake and structural alteration of gut microbiota in patients with advanced colorectal adenoma. Am. J. Clin. Nutr., 2013, 97(5), 1044-1052.
[http://dx.doi.org/10.3945/ajcn.112.046607] [PMID: 23553152]
[16]
Kostic, A.D.; Gevers, D.; Pedamallu, C.S.; Michaud, M.; Duke, F.; Earl, A.M.; Ojesina, A.I.; Jung, J.; Bass, A.J.; Tabernero, J.; Baselga, J.; Liu, C.; Shivdasani, R.A.; Ogino, S.; Birren, B.W.; Huttenhower, C.; Garrett, W.S.; Meyerson, M. Genomic analysis identifies association of Fusobacterium with colorectal carcinoma. Genome Res., 2012, 22(2), 292-298.
[http://dx.doi.org/10.1101/gr.126573.111] [PMID: 22009990]
[17]
Shen, X.J.; Rawls, J.F.; Randall, T.A.; Burcall, L.; Mpande, C.; Jenkins, N.; Jovov, B.; Abdo, Z.; Sandler, R.S.; Keku, T.O. Molecular characterization of mucosal adherent bacteria and associations with colorectal adenomas. Gut Microbes, 2010, 1(3), 138-147.
[http://dx.doi.org/10.4161/gmic.1.3.12360] [PMID: 20740058]
[18]
Wang, T.; Cai, G.; Qiu, Y.; Fei, N.; Zhang, M.; Pang, X.; Jia, W.; Cai, S.; Zhao, L. Structural segregation of gut microbiota between colorectal cancer patients and healthy volunteers. ISME J., 2012, 6(2), 320-329.
[http://dx.doi.org/10.1038/ismej.2011.109] [PMID: 21850056]
[19]
Chen, J.; Pitmon, E.; Wang, K. Microbiome, inflammation and colorectal cancer. Semin. Immunol., 2017, 32, 43-53.
[http://dx.doi.org/10.1016/j.smim.2017.09.006] [PMID: 28982615]
[20]
Ma, J.; Gao, G.; Lu, H.; Fang, D.; Li, L.; Wei, G.; Chen, A.; Yang, Y.; Zhang, H.; Huo, J. Reversal effect of ginsenoside Rh2 on oxaliplatin-resistant colon cancer cells and its mechanism. Exp. Ther. Med., 2019, 18(1), 630-636.
[http://dx.doi.org/10.3892/etm.2019.7604] [PMID: 31258699]
[21]
Santi, G.; Michetti, P.; Froehlich, F.; Rossel, J.B.; Pittet, V.; Maillard, M.H. Adherence to recommendations and quality of endoscopic colorectal cancer surveillance in long-standing ulcerative colitis. Inflamm. Intest. Dis., 2021, 6(1), 25-31.
[http://dx.doi.org/10.1159/000511010] [PMID: 33850836]
[22]
Francescone, R.; Hou, V.; Grivennikov, S.I. Cytokines, IBD, and colitis-associated cancer. Inflamm. Bowel Dis., 2015, 21(2), 409-418.
[http://dx.doi.org/10.1097/MIB.0000000000000236] [PMID: 25563695]
[23]
Kim, S.; Keku, T.O.; Martin, C.; Galanko, J.; Woosley, J.T.; Schroeder, J.C.; Satia, J.A.; Halabi, S.; Sandler, R.S. Circulating levels of inflammatory cytokines and risk of colorectal adenomas. Cancer Res., 2008, 68(1), 323-328.
[http://dx.doi.org/10.1158/0008-5472.CAN-07-2924] [PMID: 18172326]
[24]
Song, M.; Mehta, R.S.; Wu, K.; Fuchs, C.S.; Ogino, S.; Giovannucci, E.L.; Chan, A.T. Plasma inflammatory markers and risk of advanced colorectal adenoma in women. Cancer Prev. Res., 2016, 9(1), 27-34.
[http://dx.doi.org/10.1158/1940-6207.CAPR-15-0307] [PMID: 26511487]
[25]
Knüpfer, H.; Preiss, R. Serum interleukin-6 levels in colorectal cancer patients-a summary of published results. Int. J. Colorectal Dis., 2010, 25(2), 135-140.
[http://dx.doi.org/10.1007/s00384-009-0818-8] [PMID: 19898853]
[26]
Li, W.; Xu, J.; Zhao, J.; Zhang, R. Oxaliplatin and infliximab combination synergizes in inducing colon cancer regression. Med. Sci. Monit., 2017, 23, 780-789.
[http://dx.doi.org/10.12659/MSM.901880] [PMID: 28190020]
[27]
Vital, M.; Howe, A.C.; Tiedje, J.M. Revealing the bacterial butyrate synthesis pathways by analyzing (meta)genomic data. MBio, 2014, 5(2), e00889-14.
[http://dx.doi.org/10.1128/mBio.00889-14] [PMID: 24757212]
[28]
Cani, P.D.; de Vos, W.M. Next-generation beneficial microbes: The case of Akkermansia muciniphila. Front. Microbiol., 2017, 8, 1765.
[http://dx.doi.org/10.3389/fmicb.2017.01765] [PMID: 29018410]
[29]
Zoetendal, E.G.; Plugge, C.M.; Akkermans, A.D.L.; de Vos, W.M. Victivallis vadensis gen. nov., sp. nov., a sugar-fermenting anaerobe from human faeces. Int. J. Syst. Evol. Microbiol., 2003, 53(1), 211-215.
[http://dx.doi.org/10.1099/ijs.0.02362-0] [PMID: 12656175]
[30]
Tian, Y.; Xu, Q.; Sun, L.; Ye, Y.; Ji, G. Short-chain fatty acids administration is protective in colitis-associated colorectal cancer development. J. Nutr. Biochem., 2018, 57, 103-109.
[http://dx.doi.org/10.1016/j.jnutbio.2018.03.007] [PMID: 29694938]
[31]
Niccolai, E.; Baldi, S.; Ricci, F.; Russo, E.; Nannini, G.; Menicatti, M.; Poli, G.; Taddei, A.; Bartolucci, G.; Calabrò, A.S.; Stingo, F.C.; Amedei, A. Evaluation and comparison of short chain fatty acids composition in gut diseases. World J. Gastroenterol., 2019, 25(36), 5543-5558.
[http://dx.doi.org/10.3748/wjg.v25.i36.5543] [PMID: 31576099]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy