Identification of the active substances and mechanisms of ginger for the treatment of colon cancer based on network pharmacology and molecular docking

BioData Mining - Tập 14 Số 1 - 2021
Mengmeng Zhang1, Dan Wang1, Liang Feng1, Rong Zhao1, Xun Ye1, Lin He1, Li Ai2, Chunjie Wu1
1School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, P. R. China
2School of Ethnic Medicine, Chengdu University of Traditional Chinese Medicine, Chengdu, P. R. China

Tóm tắt

Abstract Background and objective

Colon cancer is occurring at an increasing rate and ginger (Zingiber officinale), as a commonly used herbal medicine, has been suggested as a potential agent for colon cancer. This study was aimed to identify the bioactive components and potential mechanisms of ginger for colon cancer prevention by an integrated network pharmacology approach.

Methods

The putative ingredients of ginger and its related targets were discerned from the TCMSP  and Swiss target prediction database. After that, the targets interacting with colon cancer were collected using Genecards, OMIM, and Drugbank databases. KEGG pathway and GO enrichment analysis were performed to explore the signaling pathways related to ginger for colon cancer treatments. The PPI and compound-target-disease networks were constructed using Cytoscape 3.8.1. Finally, Discovery studio software was employed to confirm the key genes and active components from ginger.

Results

Six potential active compounds, 285 interacting targets in addition to 1356 disease-related targets were collected, of which 118 intersection targets were obtained. A total of 34 key targets including PIK3CA, SRC, and TP53 were identified through PPI network analysis. These targets were mainly focused on the biological processes of phosphatidylinositol 3-kinase signaling, cellular response to oxidative stress, and cellular response to peptide hormone stimulus. The KEGG enrichment manifested that three signaling pathways were closely related to colon cancer prevention of ginger, cancer, endocrine resistance, and hepatitis B pathways. TP53, HSP90AA1, and JAK2 were viewed as the most important genes, which were validated by molecular docking simulation.

Conclusion

This study demonstrated that ginger produced preventive effects against colon cancer by regulating multi-targets and multi-pathways with multi-components. And, the combined data provide novel insight for ginger compounds developed as new drug for anti-colon cancer.

Từ khóa


Tài liệu tham khảo

Jemal A, Bray F, Center MM, et al. Global cancer 536 statistics. CA Cancer J Clin. 2011;61:69–90.

Nasir A, Bullo MMH, Ahmed Z, et al. Nutrigenomics: epigenetics and cancer prevention: a comprehensive review. Crit Rev Food Nutr. 2020;60(8):1375–87.

Gordaliza M. Natural products as leads to anticancer drugs. Clin Transl Oncol. 2007;9:767–76.

Govindarajan VS. Ginger: chemistry, technology, and quality evaluation: part 1. Crit Rev Food Sci. 1982;17:1–96.

Guo T, Tan SB, Wang Y, et al. Two new monoterpenoid glycosides from the fresh rhizome of Tongling white ginger (Zingiber officinale). Nat Prod Res. 2018;32:71–6.

Kubra IR, Mohan LJ. An impression on current developments in the technology, chemistry, and biological activities of ginger (Zingiber officinale roscoe). Crit Rev Food Technol. 2012;52:651–88.

Liao DW, Cheng C, Liu JP, et al. Characterization and antitumor activities of polysaccharides obtained from ginger (Zingiber officinale) by different extraction methods. Int J Biol Macromol. 2020;152:894–903.

Zhang MZ, Xiao B, Wang H, et al. Edible ginger-derived Nano-lipids loaded with doxorubicin as a novel drug-delivery approach for colon cancer therapy. Mol Ther. 2016;24:1783–96.

Song XQ, Zhang Y, Dai EQ, et al. Prediction of triptolide targets in rheumatoid arthritis using network pharmacology and molecular docking. Int Immunopharmacol. 2020;80:106179.

Kim SK, Lee S, Lee MK, et al. A systems pharmacology approach to investigate the mechanism of Oryeong-sanformula for the treatment of hypertension. J Ethnopharmacol. 2019;244:112–29.

Liu SY, Wu JR, Zhu YL, et al. Network pharmacology-based approach to investigate the mechanisms of Shenqi Fuzheng injection in the treatment of breast cancer. Eur J Integr Med. 2020;34:101064.

Ru JL, Li P, Wang JN, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. J Cheminf. 2014;6:13.

Qian C, Zhang YL, Ma YH, et al. A network pharmacology approach to investigate the mechanism of Shuxuening injection in the treatment of ischemic stroke. J Ethnopharmacol. 2020;257:112891.

Gfeller D, Grosdidier A, Wirth M, et al. SwissTargetPredicition: a web server for target predicition of bioactive small molecules. Nucleic Acids Res. 2014;42:W32–8 Web Server issue.

Stelzer G, Dalah I, Stein TI, et al. In-silico human genomics with GeneCards. Hum Genom. 2011;5(6):709–17.

Amberger JS, Bocchini CA, Schiettecatte F, et al. OMIM.org: online mendelian inheritance in man, an online catalog of human genes and genetic disorders. Nucleic Acids Res. 2015;43:D789–98.

Szklarczyk D, Franceschini A, Kuhn M, et al. STRING v11: protein-protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019;47:D607–13.

Kohl M, Wiese S, Warscheid B. Cytoscape: software for visualization and analysis of biological networks (M)//data mining in proteomics. Methods Mol Biol. 2011;96:291–303.

Kumara M, Shylajab MR, Nazeemc PA, et al. 6-Gingerol is the most potent anticancerous compound in ginger (Zingiber officinale Rosc.). J Develop Drugs. 2017;6:1–10.

Jeong CH, Bode AM, Pugliese A, et al. [6]-Gingerol suppresses colon cancer growth by targeting leukotriene A4 hydrolase. Cancer Res. 2009;69(13):5584–91.

Lin CB, Lin CC, Gregory JT. 6-Gingerol inhibits growth of colon cancer cell LoVo via induction of G2/M arrest. Evid Based Complement Alternat Med. 2012;2012:326096.

Choi YH, Kong KR, Kim YA, et al. Induction of Bax and activation of Caspases during beta-sitosterol-mediated apoptosis in human colon cancer cells. Int J Oncol. 2003;23(6):1657–62.

Wang LY, Bo XT, Yi XY, et al. Exosome-transferred LINC01559 promotes the progression of gastric cancer via PI3K/AKT signaling pathway. Cell Death Dis. 2020;11(9):723.

Li XF, Tian RF, Liu L, et al. Andrographolide enhanced radiosensitivity by downregulating glycolysis via the inhibition of the PI3K-Akt-mTOR signaling pathway in HCT116 colorectal cancer cells. J Int Med Res. 2020;48(8):1–17.

Chen Y, Wu J, Yan HF, et al. Lymecycline reverses acquired EGFR-TKI resistance in non-small-cell lung cancer by targeting GRB2. Pharmacol Res. 2020;159:105007.

Shanmugapriya K, Kim H, Kang HW. Epidermal growth factor receptor conjugated fucoidan/alginates loaded hydrogel for activating EGFR/AKT signaling pathways in colon cancer cells during targeted photodynamic therapy. Int J Biol Macromol. 2020;158:1163–74.

Chen C, Liu WR, Zhang B, et al. LncRNA H19 downregulation confers erlotinib resistance through upregulation of PKM2 and phosphorylation of AKT in EGFR-mutant lung cancers. Cancer Lett. 2020;486:58–70.

Sruthi S, Nageswaran S. Curcumin induced apoptosis is mediated through oxidative stress in mutated p53 and wild type p53 colon adenocarcinoma cell lines. J Biochem Mol Toxicol. 2020;34:e22616.

Ozbolat SN, Ayna A. Chrysin suppresses HT-29 cell death induced by diclofenac through apoptosis and oxidative damage. Nutr Cancer J. 2020;1801775.

Sies H, Jones DP. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol. 2020;21:363–83.

Rhee SG. Cell signaling. H2O2 a necessary evil for cell signaling. Science. 2006;312:1882–3.

Weinberg F, Ramnath N, Nagrath D. Reactive oxygen species in the tumor microenvironment: an overview. Cancers. 2019;11:1191.