Effects of compound K, an enteric microbiome metabolite of ginseng, in the treatment of inflammation associated colon cancer

Yao,Haiqiang; Wan,Jin‑Yi; Zeng,Jinxiang; Huang,Wei‑Hua; Sava‑Segal,Clara; Li,Lingru; Niu,Xin; Wang,Qi; Wang,Chong‑Zhi; Yuan,Chun‑Su

doi:10.3892/ol.2018.8414

Effects of compound K, an enteric microbiome metabolite of ginseng, in the treatment of inflammation associated colon cancer

Authors:
- Haiqiang Yao
- Jin‑Yi Wan
- Jinxiang Zeng
- Wei‑Hua Huang
- Clara Sava‑Segal
- Lingru Li
- Xin Niu
- Qi Wang
- Chong‑Zhi Wang
- Chun‑Su Yuan
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Affiliations: School of Basic Medical Science, Beijing University of Chinese Medicine, Beijing 100029, P.R. China, Tang Center for Herbal Medicine Research, University of Chicago, Chicago, IL 60637, USA
Published online on: April 2, 2018 https://doi.org/10.3892/ol.2018.8414
Pages: 8339-8348
Copyright: © Yao et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Ginsenoside Rb1, a major component of different ginseng species, can be bioconverted into compound K by gut microbiota, and the latter possess much stronger cancer chemopreventive potential. However, while the initiation and progression of colorectal cancer is closely associated with gut inflammation, to date, the effects of compound K on inflammation‑linked cancer chemoprevention have not been reported. In the present study, liquid chromatography quadrupole time‑of‑flight mass spectrometry analysis was applied to evaluate the biotransformation of Rb1 in American ginseng by human enteric microflora. The in vitro inhibitory effects of Rb1 and compound K were compared using the HCT‑116 and HT‑19 human colorectal cancer cell lines by a MTS assay. Cell cycle and cell apoptosis were assayed using flow cytometry. Using ELISA, the anti‑inflammatory effects of Rb1 and compound K were compared for their inhibition of interleukin‑8 secretion in HT‑29 cells, induced by lipopolysaccharide. The results revealed that compound K is the major intestinal microbiome metabolite of Rb1. When compared with Rb1, compound K had significantly stronger anti‑proliferative effects in HCT‑116 and HT‑29 cell lines (P<0.01). Compound K significantly arrested HCT‑116 and HT‑29 cells in the G1 phase, and induced cell apoptosis (P<0.01). By contrast, Rb1 did not markedly influence the cell cycle or apoptosis. Furthermore, compound K exerted significant anti‑inflammatory effects even at low concentrations (P<0.05), while Rb1 did not have any distinct effects. The data obtained from the present study demonstrated that compound K, an intestinal microbiome metabolite of Rb1, may have a potential clinical value in the prevention of inflammatory‑associated colorectal cancer.

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1	Qi LW, Wang CZ and Yuan CS: Isolation and analysis of ginseng: Advances and challenges. Nat Prod Rep. 28:467–495. 2011. View Article : Google Scholar : PubMed/NCBI
2	Kim DH: Chemical Diversity of Panax ginseng, Panax quinquifolium, and Panax notoginseng. J Ginseng Res. 36:1–15. 2012. View Article : Google Scholar : PubMed/NCBI
3	Park J, Bui PTC, Song H, Kim SK, Rhee DK, Kim EY, Rhyu MR, Lee MS and Lee YJ: Ginseng on nuclear hormone receptors. Am J Chin Med. 45:1147–1156. 2017. View Article : Google Scholar : PubMed/NCBI
4	Yennurajalingam S, Tannir NM, Williams JL, Lu Z, Hess KR, Frisbee-Hume S, House HL, Lim ZD, Lim KH, Lopez G, et al: A double-blind, randomized, placebo-controlled trial of Panax ginseng for cancer-related fatigue in patients with advanced cancer. J Natl Compr Canc Netw. 15:1111–1120. 2017. View Article : Google Scholar : PubMed/NCBI
5	Wan JY, Huang WH, Zheng W, Park CW, Kim SH, Seo DB, Shin KS, Zeng JX, Yao H, Sava-Segal C, et al: Multiple effects of ginseng berry polysaccharides: Plasma cholesterol level reduction and enteric neoplasm prevention. Am J Chin Med. 45:1293–1307. 2017. View Article : Google Scholar : PubMed/NCBI
6	Qi LW, Wang CZ and Yuan CS: Ginsenosides from American ginseng: Chemical and pharmacological diversity. Phytochemistry. 72:689–699. 2011. View Article : Google Scholar : PubMed/NCBI
7	Yuan CS, Wang CZ, Wicks SM and Qi LW: Chemical and pharmacological studies of saponins with a focus on American ginseng. J Ginseng Res. 34:160–167. 2010. View Article : Google Scholar : PubMed/NCBI
8	Lee SJ, Ha N, Kim Y and Kim MG: Changes in the ginsenoside content during fermentation using an appliance for the preparation of red ginseng. Am J Chin Med. 44:1595–1606. 2016. View Article : Google Scholar : PubMed/NCBI
9	Du XH, Zhao YL, Yang DF, Liu Y, Fan K, Liang ZS and Han RL: A correlation model of UPLC fingerprints and anticoagulant activity for quality assessment of Panax notoginseng by hierarchical clustering analysis and multiple linear regression analysis. Anal Met. 7:2985–2992. 2015. View Article : Google Scholar
10	Wan JY, Liu P, Wang HY, Qi LW, Wang CZ, Li P and Yuan CS: Biotransformation and metabolic profile of American ginseng saponins with human intestinal microflora by liquid chromatography quadrupole time-of-flight mass spectrometry. J Chromatogr A. 1286:83–92. 2013. View Article : Google Scholar : PubMed/NCBI
11	Xiao J, Chen H, Kang D, Shao Y, Shen B, Li X, Yin X, Zhu Z, Li H, Rao T, et al: Qualitatively and quantitatively investigating the regulation of intestinal microbiota on the metabolism of Panax notoginseng saponins. J Ethnopharmacol. 194:324–336. 2016. View Article : Google Scholar : PubMed/NCBI
12	Hu Z, Yang J, Cheng C, Huang Y, Du F, Wang F, Niu W, Xu F, Jiang R, Gao X and Li C: Combinatorial metabolism notably affects human systemic exposure to ginsenosides from orally administered extract of Panax notoginseng roots (Sanqi). Drug Metab Dispos. 41:1457–1469. 2013. View Article : Google Scholar : PubMed/NCBI
13	Wan JY, Wang CZ, Liu Z, Zhang QH, Musch MW, Bissonnette M, Chang EB, Li P, Qi LW and Yuan CS: Determination of American ginseng saponins and their metabolites in human plasma, urine and feces samples by liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 1015–1016:62–73. 2016. View Article : Google Scholar
14	Wang CZ, Kim KE, Du GJ, Qi LW, Wen XD, Li P, Bauer BA, Bissonnette MB, Musch MW, Chang EB and Yuan CS: Ultra-performance liquid chromatography and time-of-flight mass spectrometry analysis of ginsenoside metabolites in human plasma. Am J Chin Med. 39:1161–1171. 2011. View Article : Google Scholar : PubMed/NCBI
15	Wang CZ, Du GJ, Zhang Z, Wen XD, Calway T, Zhen Z, Musch MW, Bissonnette M, Chang EB and Yuan CS: Ginsenoside compound K, not Rb1, possesses potential chemopreventive activities in human colorectal cancer. Int J Oncol. 40:1970–1976. 2012.PubMed/NCBI
16	Grimoud J, Durand H, de Souza S, Monsan P, Ouarné F, Theodorou V and Rogues C: In vitro screening of probiotics and synbiotics according to anti-inflammatory and anti-proliferative effects. Int J Food Microbiol. 144:42–50. 2010. View Article : Google Scholar : PubMed/NCBI
17	Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 136:E359–E386. 2015. View Article : Google Scholar : PubMed/NCBI
18	Troeung L, Sodhi-Berry N, Martini A, Malacova E, Ee H, O'Leary P, Lansdorp-Vogelaar I and Preen DB: Increasing incidence of colorectal cancer in adolescents and young adults aged 15–39 years in Western Australia 1982–2007: Examination of colonoscopy history. Front Public Health. 5:1792017. View Article : Google Scholar : PubMed/NCBI
19	Campos FGCM, Figueiredo MN, Monteiro M, Nahas SC and Cecconello I: Incidence of colorectal cancer in young patients. Rev Col Bras Cir. 44:208–215. 2017.(In English, Portuguese). View Article : Google Scholar : PubMed/NCBI
20	Ullman TA and Itzkowitz SH: Prognosis of colorectal cancer in inflammatory bowel disease: Data from a state registry. Dig Dis Sci. 62:1850–1851. 2017. View Article : Google Scholar : PubMed/NCBI
21	Ehrlich AC, Patel S, Meillier A, Rothstein RD and Friedenberg FK: Chemoprevention of colorectal cancer in inflammatory bowel disease. Expert Rev Anticancer Ther. 17:247–255. 2017. View Article : Google Scholar : PubMed/NCBI
22	Brennan CA and Garrett WS: Gut microbiota, inflammation, and colorectal cancer. Annu Rev Microbiol. 70:395–411. 2016. View Article : Google Scholar : PubMed/NCBI
23	Wang CZ, Huang WH, Zhang CF, Wan JY, Wang Y, Yu C, Williams S, He TC, Du W, Musch MW, et al: Role of intestinal microbiome in American ginseng-mediated colon cancer protection in high fat diet-fed AOM/DSS mice. Clin Transl Oncol. 20:302–312. 2018. View Article : Google Scholar : PubMed/NCBI
24	Dai D, Zhang CF, Williams S, Yuan CS and Wang CZ: Ginseng on cancer: Potential role in modulating inflammation-mediated angiogenesis. Am J Chin Med. 45:13–22. 2017. View Article : Google Scholar : PubMed/NCBI
25	Kim HS, Kim MK, Lee M, Kwon BS, Suh DH and Song YS: Effect of red ginseng on genotoxicity and health-related quality of life after adjuvant chemotherapy in patients with epithelial ovarian cancer: A randomized, double blind, placebo-controlled trial. Nutrients. 9:pii: E772. 2017. View Article : Google Scholar
26	Yu T, Rhee MH, Lee J, Kim SH, Yang Y, Kim HG, Kim Y, Kim C, Kwak YS, Kim JH and Cho JY: Ginsenoside Rc from Korean red ginseng (Panax ginseng C.A. Meyer) attenuates inflammatory symptoms of gastritis, hepatitis and arthritis. Am J Chin Med. 44:595–615. 2016. View Article : Google Scholar : PubMed/NCBI
27	Poudyal D, Le PM, Davis T, Hofseth AB, Chumanevich A, Chumanevich AA, Wargovich MJ, Nagarkatti M, Nagarkatti PS, Windust A and Hofseth LJ: A hexane fraction of American ginseng suppresses mouse colitis and associated colon cancer: Anti-inflammatory and proapoptotic mechanisms. Cancer Prev Res (Phila). 5:685–696. 2012. View Article : Google Scholar : PubMed/NCBI
28	Tawab MA, Bahr U, Karas M, Wurglics M and Schubert-Zsilavecz M: Degradation of ginsenosides in humans after oral administration. Drug Metab Dispos. 31:1065–1071. 2003. View Article : Google Scholar : PubMed/NCBI
29	Kim KA, Jung IH, Park SH, Ahn YT, Huh CS and Kim DH: Comparative analysis of the gut microbiota in people with different levels of ginsenoside Rb1 degradation to compound K. PLoS One. 8:e624092013. View Article : Google Scholar : PubMed/NCBI
30	Xiao J, Chen D, Lin XX, Peng SF, Xiao MF, Huang WH, Wang YC, Peng JB, Zhang W, Ouyang DS and Chen Y: Screening of drug metabolizing enzymes for the ginsenoside compound K in vitro: An efficient anti-cancer substance originating from Panax ginseng. PLoS One. 11:e01471832016. View Article : Google Scholar : PubMed/NCBI
31	Chen Y, Xu Y, Zhu Y and Li X: Anti-cancer effects of ginsenoside compound K on pediatric acute myeloid leukemia cells. Cancer Cell Int. 13:242013. View Article : Google Scholar : PubMed/NCBI