A Study Against Colon Cancer Mechanism of Xanthium sibiricum Herba Based on Computer Simulation and Bioinformatics


Цитировать

Полный текст

Аннотация

Introduction:Cancer is one of the leading causes of death worldwide, accounting for nearly one in six deaths in 2020. As a folk medicine, Xanthium sibiricum Herba (XSH) has been used many times in clinical practice for the treatment of various diseases. With the increasing number of cancer patients, there is a clinical need to find effective anti-cancer drugs.

Aim:This study aims to explores the bioactivity and the anti-cancer mechanism of XSH.

Methods:In this study, bioinformatics, network pharmacology, molecular docking, molecular dynamics simulation techniques, and apoptosis assay were used to explore the bioactivity and the anti- cancer mechanism of XSH.

Results:Finally, seven active ingredients in XSH after the screening were obtained, the two most active compounds were β-sitosterol and aloe-emodin, and good anti-cancer activity of XSH was predicted.

Discussion:Four core targets were obtained from the PPI network map, namely Caspase-3 (CASP3), Transcription factor AP-1 (JUN), Myc proto-oncogene protein (MYC), and cellular tumor antigen p53 (TP53). GO and KEGG analyses showed that the mechanism of XSH anti-cancer is mainly related to the apoptosis process, and the main signaling pathways are enriched in the p53 signaling pathway, Apoptosis, and MAPK signaling. The molecular docking and molecular dynamics simulation results showed that CASP3, JUN, MYC, and TP53 had a high affinity with β- sitosterol and aloe-emodin. Bioinformatics analyses demonstrated the importance of core targets. Apoptosis assay showed that XSH could significantly promote the apoptosis of cancer cells, and inhibit their proliferation and migration, especially colon cancer cells.

Conclusion:This study uncovered the main active components, bioactivities, and potential targets of XSH, and further revealed the multi-component, multi-target, and multi-pathway mechanism of XSH for cancer treatment and promoting apoptosis.

Об авторах

Ying Qi

Traditional Chinese Medicine College,, Guangdong Pharmaceutical University

Email: info@benthamscience.net

Jia-Han Cai

Traditional Chinese Medicine College, Guangdong Pharmaceutical University

Email: info@benthamscience.net

Qiu-Tong Deng

Traditional Chinese Medicine College, Guangdong Pharmaceutical University

Email: info@benthamscience.net

Yuan-Ning Zeng

Traditional Chinese Medicine College, Guangdong Pharmaceutical University

Email: info@benthamscience.net

Qiu-Hong Wang

Traditional Chinese Medicine College, Guangdong Pharmaceutical University

Автор, ответственный за переписку.
Email: info@benthamscience.net

Список литературы

  1. Jemal, A.; Siegel, R.; Xu, J.; Ward, E. Cancer Statistics, 2010. CA Cancer J. Clin., 2010, 60(5), 277-300. doi: 10.3322/caac.20073 PMID: 20610543
  2. Jing, H.; Wei, Z.; Yong, S.; Lunfang, X.; Wei, W. Psychological distress among elderly patients with cancer. Chung Hua Hu Li Tsa Chih, 2015, 50(01), 92-96. doi: 10.3761/j.issn.0254-1769.2015.01.022
  3. Weijin, W.; Xiaolu, Z. Stat-quo and disease burden of cancer in china. China Policy Review, 2019, 04, 63-73.
  4. Ying, Z.; Wei, H.; Hongsheng, L. Clinical research results and thinking of traditional chinese medicine in the treatment of malignant tumors. J. Tradit. Chin. Med., 2014, 55(06), 523-525. doi: 10.13288/j.11-2166/r.2014.06.021
  5. Yıldırım, M.A.; Goh, K.I.; Cusick, M.E.; Barabási, A.L.; Vidal, M. Drug—target network. Nat. Biotechnol., 2007, 25(10), 1119-1126. doi: 10.1038/nbt1338 PMID: 17921997
  6. Hopkins, A.L. Network pharmacology: The next paradigm in drug discovery. Nat. Chem. Biol., 2008, 4(11), 682-690. doi: 10.1038/nchembio.118 PMID: 18936753
  7. Hongjing, T. Famous doctors’ special book; People's Medical Publishing House: Beijing, 1986.
  8. Nanjing University Of Chinese Medicine. Dictionary of traditional chinese medicine; Publishers, Shanghai Scientific Technical: Shanghai, 2006.
  9. Xiaoli, J. The pharmacognosy research of herba xanthii; Chengdu University of TCM, 2011.
  10. Shen, M. Dietary herbal annotation; Shanghai Classics Publishing House: Shanghai, 2007.
  11. Chu-An, W. Materia medica is easy to read, People’s Medical Publishing House; PMPH: Beijing, 1987.
  12. Xin, T.; Ting-Ting, Z.; Mei-Jiao, C.; Qiao, C.; Nan, X. Study on the phenol constituents and antibacterial action of xanthium sibiricum. Zhong Yao Cai, 2017, 40(06), 1326-1330. doi: 10.13863/j.issn1001-4454.2017.06.019
  13. Guo, F.; Zeng, Y.; Li, J. Inhibition of α-glucosidase activity by water extracts of Xanthium sibiricum Patrin ex Widder and their effects on blood sugar in mice. Zhejiang Da Xue Xue Bao Yi Xue Ban, 2013, 42(6), 632-637. doi: 10.3785/j.issn.1008-9292.2013.06.007 PMID: 24421228
  14. Li, X.; Li, Z.; Xue, M.; Ou, Z.; Liu, M.; Yang, M.; Liu, S.; Yang, S.; Li, X.; Mihai, C. Fructus xanthii attenuates hepatic steatosis in rats fed on high-fat diet. PLoS One, 2013, 8(4), e61499. doi: 10.1371/journal.pone.0061499 PMID: 23585904
  15. Tang, J.; Aittokallio, T. Network pharmacology strategies toward multi-target anticancer therapies: from computational models to experimental design principles. Curr. Pharm. Des., 2014, 20(1), 23-36. doi: 10.2174/13816128113199990470 PMID: 23530504
  16. Ru, J.; Li, P.; Wang, J.; Zhou, W.; Li, B.; Huang, C.; Li, P.; Guo, Z.; Tao, W.; Yang, Y.; Xu, X.; Li, Y.; Wang, Y.; Yang, L. TCMSP: A database of systems pharmacology for drug discovery from herbal medicines. J. Cheminform., 2014, 6(1), 13. doi: 10.1186/1758-2946-6-13 PMID: 24735618
  17. Xu, X.; Zhang, W.; Huang, C.; Li, Y.; Yu, H.; Wang, Y.; Duan, J.; Ling, Y. A novel chemometric method for the prediction of human oral bioavailability. Int. J. Mol. Sci., 2012, 13(6), 6964-6982. doi: 10.3390/ijms13066964 PMID: 22837674
  18. Jiang, L.; Shi, Z.; Yang, Y. Network pharmacology-based approach to investigate the molecular targets of rhubarb for treating cancer. Evid. Based Complement. Alternat. Med., 2021, 2021, 9945633. doi: 10.1155/2021/9945633
  19. Zhou, Y.; Zhou, B.; Pache, L.; Chang, M.; Khodabakhshi, A.H.; Tanaseichuk, O.; Benner, C.; Chanda, S.K. Metascape provides a biologist-oriented resource for the analysis of systems-level datasets. Nat. Commun., 2019, 10(1), 1523. doi: 10.1038/s41467-019-09234-6 PMID: 30944313
  20. Szklarczyk, D.; Gable, A.L.; Nastou, K.C.; Lyon, D.; Kirsch, R.; Pyysalo, S.; Doncheva, N.T.; Legeay, M.; Fang, T.; Bork, P.; Jensen, L.J.; von Mering, C. The STRING database in 2021: Customizable protein–protein networks, and functional characterization of user-uploaded gene/measurement sets. Nucleic Acids Res., 2021, 49(D1), D605-D612. doi: 10.1093/nar/gkaa1074 PMID: 33237311
  21. Abraham, M.J.; Murtola, T.; Schulz, R.; Páll, S.; Smith, J.C.; Hess, B.; Lindahl, E. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX, 2015, 1-2, 19-25. doi: 10.1016/j.softx.2015.06.001
  22. Yuan, H.; Rui, C.; Jixiong, M.; Zhenning, C.; Yang, Z. Screening of α-glucosidase inhibitors in alpine compositae extracts. Zhongguo Yaoke Daxue Xuebao, 2008, 39(6), 4. doi: 10.3321/j.issn:1000-5048.2008.06.020
  23. Wolfe, A.; Shimer, G.H., Jr; Meehan, T. Polycyclic aromatic hydrocarbons physically intercalate into duplex regions of denatured DNA. Biochemistry, 1987, 26(20), 6392-6396. doi: 10.1021/bi00394a013 PMID: 3427013
  24. Tang, Z.; Li, C.; Kang, B.; Gao, G.; Li, C.; Zhang, Z. GEPIA: A web server for cancer and normal gene expression profiling and interactive analyses. Nucleic Acids Res., 2017, 45(W1), W98-W102. doi: 10.1093/nar/gkx247 PMID: 28407145
  25. Hsin, K.Y.; Ghosh, S.; Kitano, H.; Franca, F. Combining machine learning systems and multiple docking simulation packages to improve docking prediction reliability for network pharmacology. PLoS One, 2013, 8(12), e83922. doi: 10.1371/journal.pone.0083922 PMID: 24391846
  26. Wang, Y.; Shen, J.; He, Q.; Yang, K.L.; He, C.N.; Xiao, P.G. Material basis and mechanism of Huangqin Tea in prevention of colorectal cancer based on network pharmacology and molecular docking. Zhongguo Zhongyao Zazhi, 2021, 46(23), 6251-6260. doi: 10.19540/j.cnki.cjcmm.20210916.401 PMID: 34951252
  27. Hua, J.G.; Xiao-Li, J.; Jun, Z.; Fu-Rong, Z.; Sha, Y.; Jia-Ni, C. Antibacterial test of aqueous extract and acetone extract of xanthium sibiricum. Huaxi Yaoxue Zazhi, 2011, 26(04), 345-346. doi: 10.13375/j.cnki.wcjps.2011.04.013
  28. Lu, S.; Nuo, H.J.; Jing, Z.; Zijun, Z.; Chao, W. Research status of death cause analysis of residents in my country. J. Modern Med. Heal., 2018, 34(19), 3011-3014. doi: 10.3969/j.issn.1009-5519.2018.19.021
  29. Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell, 2011, 144(5), 646-674. doi: 10.1016/j.cell.2011.02.013 PMID: 21376230
  30. Jing, Z.; Xiaofang, L.; Yu, L.; Mingze, W. Research progress in cancer epidemiology and antitumor traditional chinese medicine. Shandong Chem. Indus., 2015, 44(12), 42-44. doi: 10.19319/j.cnki.issn.1008-021x.2015.12.020
  31. Yingchen, H. Medicinal value of cocklebur. J. Pharm. Pract., 2005, (03), 262-263. doi: 10.14172/j.cnki.issn1671-4008.2005.03.056
  32. Guiying, W.; Jikun, T. Acute toxicity test of cocklebur from guizhou. Brit. Med. J., 2018, 5(07), 164-168. doi: 10.16281/j.cnki.jocml.2018.07.137
  33. Yuan, S. Nutriology, pharmacology and cardiovascular effects of Xanthium sibiricum. Prog. Nutr., 2020, 22, 370-377.
  34. Zhang, L.; Ruan, J.; Yan, L.; Li, W.; Wu, Y.; Tao, L.; Zhang, F.; Zheng, S.; Wang, A.; Lu, Y. Xanthatin induces cell cycle arrest at G2/M checkpoint and apoptosis via disrupting NF-κB pathway in A549 non-small-cell lung cancer cells. Molecules, 2012, 17(4), 3736-3750. doi: 10.3390/molecules17043736 PMID: 22450683
  35. Takeda, S.; Matsuo, K.; Yaji, K.; Okajima-Miyazaki, S.; Harada, M.; Miyoshi, H.; Okamoto, Y.; Amamoto, T.; Shindo, M.; Omiecinski, C.J.; Aramaki, H. (--)-Xanthatin selectively induces GADD45γ and stimulates caspase-independent cell death in human breast cancer MDA-MB-231 cells. Chem. Res. Toxicol., 2011, 24(6), 855-865. doi: 10.1021/tx200046s PMID: 21568272
  36. Ya-Yun, C.; Yu, W.; Shui-Ying, Y.; Jing, M.; Gang, C.; Gang, C. Anticancer effect of xanthium in vitro and in vivo in hepg2 of hepatocellular carcinoma. Chin. J. Integr. Med., 2019, 14(07), 946-949. doi: 10.13935/j.cnki.sjzx.190715
  37. Li, W.D.; Wu, Y.; Zhang, L.; Yan, L.G.; Yin, F.Z.; Ruan, J.S.; Chen, Z.P.; Yang, G.M.; Yan, C.P.; Zhao, D.; Lu, Y.; Cai, B.C. Characterization of xanthatin: Anticancer properties and mechanisms of inhibited murine melanoma in vitro and in vivo. Phytomedicine, 2013, 20(10), 865-873. doi: 10.1016/j.phymed.2013.03.006 PMID: 23664560
  38. Zeli, M.; Dongchen, X.; Jian, G. Clinical observation on 38 cases of skin cancer treated with xanthicao ointment. J. Gansu Uni. Chinese Med., 1999, 16(1), 2.
  39. Weiliang, L.; Yu, J.; Aixiang, H. Research and development progress of β- sitosterol. Inf. Process. Agric., 2019, (01), 77-79. doi: 10.16693/j.cnki.1671-9646(X).2019.01.022
  40. Shuai, W.; Yu, S.; Chunmei, L.; Qun, L. Research progress of stigmasterol. China Pharmaceuticals, 2019, 28(23), 96-98. doi: 10.3969/j.issn.1006-4931.2019.23.031
  41. Simin, F.; Ke, N.; Ping, S.; Guoping, R.; Peilong, S.; Zisheng, L. Research on the β-sitosterol and stigmasterol therapeutic effect of acute colitis in mice. J. Chin. Cereals Oils Assoc., 2018, 33(12), 80-86. doi: 10.3969/j.issn.1003-0174.2018.12.014
  42. Mu, L. Du Zhi-min, Research progress on pharmacological effects of aloe -emodin. Chin. J. Pharmacol., 2015, 31(09), 765-768. doi: 10.13699/j.cnki.1001-6821.2015.09.027
  43. Zhang-Bin, T.; You-Cai, X.; Wen-Jun, D.; Sui-Hui, D.; Bin, L.; Jing-Zhi, Z. Mechanism of aloe-emodin in inhibiting proliferation and migration of hepatocellular carcinoma cells. Zhongchengyao, 2021, 43(10), 2653-2658. doi: 10.3969/j.issn.1001-1528.2021.10.009
  44. Chang, H.W.; Liu, P.F.; Tsai, W.L.; Hu, W.H.; Hu, Y.C.; Yang, H.C.; Lin, W.Y.; Weng, J.R.; Shu, C.W. Shu, Xanthium strumarium fruit extract inhibits atg4b and diminishes the proliferation and metastatic characteristics of colorectal cancer cells. Toxins, 2019, 11(6), 313. doi: 10.3390/toxins11060313 PMID: 31159487
  45. Xiaohong, P.; Qing, Y. Dysfunction of the tp53 in some lymphoid malignancies and blood cancer. Linchuang Zhongliuxue Zazhi, 2014, 19(02), 186-190.
  46. Gong, Z.J.; Huang, H.B.; Xu, K.; Liang, F.; Li, X.L.; Xiong, W.; Zeng, Z.Y.; Li, G.Y. Advances in micrornas and tp53 gene regulatory network. Sheng Wu Hua Xue Yu Sheng Wu Wu Li Jin Zhan, 2013, 39(12), 1133-1144. doi: 10.3724/SP.J.1206.2012.00015
  47. Bin Sayeed, M.S.; Ameen, S.S. Beta-sitosterol: A promising but orphan nutraceutical to fight against cancer. Nutr. Cancer, 2015, 67(8), 1216-1222. doi: 10.1080/01635581.2015.1087042 PMID: 26473555
  48. Wang, Z.; Zhan, Y.; Xu, J.; Wang, Y.; Sun, M.; Chen, J.; Liang, T.; Wu, L.; Xu, K. B-sitosterol reverses multidrug resistance via bcrp suppression by inhibiting the p53–mdm2 interaction in colorectal cancer. J. Agric. Food Chem., 2020, 68(12), 3850-3858. doi: 10.1021/acs.jafc.0c00107 PMID: 32167760
  49. Bae, H.; Park, S.; Ham, J.; Song, J.; Hong, T.; Choi, J.H.; Song, G.; Lim, W. Er-mitochondria calcium flux by β-sitosterol promotes cell death in ovarian cancer. Antioxidants, 2021, 10(10), 1583. doi: 10.3390/antiox10101583 PMID: 34679718
  50. Qiang, Z.; Xin-Huai, Z. Phytosterol and its anticancer effect. Zhongguo Youzhi, 2006, (10), 57-60.
  51. Qian, K.; Zheng, X.X.; Wang, C.; Huang, W.G.; Liu, X.B.; Xu, S.D.; Liu, D.K.; Liu, M.Y.; Lin, C.S. B-sitosterol inhibits rheumatoid synovial angiogenesis through suppressing vegf signaling pathway. Front. Pharmacol., 2022, 12, 816477. doi: 10.3389/fphar.2021.816477 PMID: 35295740
  52. Sharmila, R.; Sindhu, G. Modulation of angiogenesis, proliferative response and apoptosis by β-sitosterol in rat model of renal carcinogenesis. Indian J. Clin. Biochem., 2017, 32(2), 142-152. doi: 10.1007/s12291-016-0583-8 PMID: 28428688
  53. Lin, K.Y.; Uen, Y.H. Aloe-emodin, an anthraquinone, in vitro inhibits proliferation and induces apoptosis in human colon carcinoma cells. Oncol. Lett., 2010, 1(3), 541-547. doi: 10.3892/ol_00000096 PMID: 22966340
  54. Jiang, D.; Ding, S.; Mao, Z.; You, L.; Ruan, Y. Integrated analysis of potential pathways by which aloe-emodin induces the apoptosis of colon cancer cells. Cancer Cell Int., 2021, 21(1), 238. doi: 10.1186/s12935-021-01942-8 PMID: 33902610
  55. Abdellatef, A.A.; Fathy, M.; Mohammed, A.E.S.I.; Bakr, M.S.A.; Ahmed, A.H.; Abbass, H.S.; El-Desoky, A.H.; Morita, H.; Nikaido, T.; Hayakawa, Y. Inhibition of cell-intrinsic NF-κB activity and metastatic abilities of breast cancer by aloe-emodin and emodic-acid isolated from Asphodelus microcarpus. J. Nat. Med., 2021, 75(4), 840-853. doi: 10.1007/s11418-021-01526-w PMID: 33988779
  56. Suboj, P.; Babykutty, S.; Valiyaparambil Gopi, D.R.; Nair, R.S.; Srinivas, P.; Gopala, S. Aloe emodin inhibits colon cancer cell migration/angiogenesis by downregulating MMP-2/9, RhoB and VEGF via reduced DNA binding activity of NF-κB. Eur. J. Pharm. Sci., 2012, 45(5), 581-591. doi: 10.1016/j.ejps.2011.12.012 PMID: 22227305

Дополнительные файлы

Доп. файлы
Действие
1. JATS XML
Скачать

© Bentham Science Publishers, 2024