Network Analysis Reveals Tea Catechins as Multi-Target Inhibitors of Colon Adenocarcinoma

Authors

  • Anwar Rovik Universitas Gadjah Mada
  • Dyah Fitri Kusharyati Universitas Jenderal Soedirman

DOI:

https://doi.org/10.30595/jrst.v9i2.23742

Keywords:

Chemoprevention, Colon Cancer, EGCG, Ethnopharmacology, Tea Catechin

Abstract

Colon cancer is the second most common cause of cancer death worldwide. It drives the need for effective prevention and treatment strategies, including identifying new and inventive targets for treating colon cancer. This present study evaluated the potential of tea catechins against colon adenocarcinoma in silico. The study method includes a literature review, an analysis of protein targets and protein interactions, and network analysis. The prediction analysis showed that only epicatechin-3-gallate, epigallocatechin-3-gallate, and epigallocatechin potentially target colon cancer. These compounds target six common proteins in human cancer cells, such as AURKA, CA9, SERPINE1, MET, SQLE, and VEGFA. The analysis showed that the protein targets interact strongly with various proteins in human cancer cells. Therefore, tea catechin, especially epigallocatechin-3-gallate, can be explored as a colon cancer chemopreventive agent.

References

Abe, I., Seki, T., Umehara, K., Miyase, T., Noguchi, H., Sakakibara, J., & Ono, T. (2000). Green Tea Polyphenols: Novel and Potent Inhibitors of Squalene Epoxidase. Biochemical and Biophysical Research Communications, 268(3), 767–771. https://doi.org/10.1006/bbrc.2000.2217

Anand, U., Dey, A., Chandel, A. K. S., Sanyal, R., Mishra, A., Pandey, D. K., De Falco, V., Upadhyay, A., Kandimalla, R., Chaudhary, A., Dhanjal, J. K., Dewanjee, S., Vallamkondu, J., & Pérez De La Lastra, J. M. (2023). Cancer Chemotherapy and Beyond: Current Status, Drug Candidates, Associated Risks and Progress in Targeted Therapeutics. Genes & Diseases, 10(4), 1367–1401. https://doi.org/10.1016/j.gendis.2022.02.007

Anyanwu, O. A., Naumova, E. N., Chomitz, V. R., Zhang, F.-F., Chui, K., Kartasurya, M. I., & Folta, S. C. (2022). The Socio-Ecological Context of the Nutrition Transition in Indonesia: A Qualitative Investigation of Perspectives from Multi-Disciplinary Stakeholders. Nutrients, 15(1), 25. https://doi.org/10.3390/nu15010025

Azwar, S., Seow, H. F., Abdullah, M., Faisal Jabar, M., & Mohtarrudin, N. (2021). Recent Updates on Mechanisms of Resistance to 5-Fluorouracil and Reversal Strategies in Colon Cancer Treatment. Biology, 10(9), 854. https://doi.org/10.3390/biology10090854

Cerezo-Guisado, M. I., Zur, R., Lorenzo, M. J., Risco, A., Martín-Serrano, M. A., Alvarez-Barrientos, A., Cuenda, A., & Centeno, F. (2015). Implication of Akt, ERK1/2, and Alternative p38MAPK Signalling Pathways in Human Colon Cancer Cell Apoptosis Induced by Green Tea EGCG. Food and Chemical Toxicology, 84, 125–132. https://doi.org/10.1016/j.fct.2015.08.017

Cháirez-Ramírez, M. H., De La Cruz-López, K. G., & García-Carrancá, A. (2021). Polyphenols as Antitumor Agents Targeting Key Players in Cancer-Driving Signaling Pathways. Frontiers in Pharmacology, 12, 710304. https://doi.org/10.3389/fphar.2021.710304

Cheng, Z., Zhang, Z., Han, Y., Wang, J., Wang, Y., Chen, X., Shao, Y., Cheng, Y., Zhou, W., Lu, X., & Wu, Z. (2020). A Review on Anticancer Effect of Green Tea Catechins. Journal of Functional Foods, 74, 104172. https://doi.org/10.1016/j.jff.2020.104172

Clarke, J. M., & Hurwitz, H. I. (2013). Understanding and Targeting Resistance to Anti-angiogenic Therapies. Journal of Gastrointestinal Oncology, 4(3), 253–263. https://doi.org/10.3978/j.issn.2078-6891.2013.036

Du, Y., Rokavec, M., & Hermeking, H. (2023). Squalene Epoxidase/SQLE is A Candidate Target for Treatment of Colorectal Cancers with P53 Mutation and Elevated C-MYC Expression. International Journal of Biological Sciences, 19(13), 4103–4122. https://doi.org/10.7150/ijbs.85724

Farhan, M. (2022). Green Tea Catechins: Nature’s Way of Preventing and Treating Cancer. International Journal of Molecular Sciences, 23(18), 10713. https://doi.org/10.3390/ijms231810713

Ferlay, J., Soerjomataram, I., Dikshit, R., Eser, S., Mathers, C., Rebelo, M., Parkin, D. M., Forman, D., & Bray, F. (2015). Cancer Incidence and Mortality Worldwide: Sources, Methods and Major Patterns in GLOBOCAN 2012. International Journal of Cancer, 136(5), E359-386. https://doi.org/10.1002/ijc.29210

Guo, Z., Jiang, M., Luo, W., Zheng, P., Huang, H., & Sun, B. (2019). Association of Lung Cancer and Tea-Drinking Habits of Different Subgroup Populations: Meta-Analysis of Case-Control Studies and Cohort Studies. Iranian Journal of Public Health, 48(9), 1566–1576. https://pmc.ncbi.nlm.nih.gov/articles/PMC6825660/

Hutajulu, S. H., Paramita, D. K., Santoso, J., Sani, M. I. A., Amalia, A., Wulandari, G., Ghozali, A., & Kurnianda, J. (2018). Correlation Between Vascular Endothelial Growth Factor-A Expression and Tumor Location and Invasion in Patients with Colorectal Cancer. Journal of Gastrointestinal Oncology, 9(6), 1099–1108. https://doi.org/10.21037/jgo.2018.07.01

Kang, Y., Li, H., Liu, Y., & Li, Z. (2024). Regulation of VEGF-A Expression and VEGF-A Targeted Therapy in Malignant Tumors. Journal of Cancer Research and Clinical Oncology, 150(5), 221. https://doi.org/10.1007/s00432-024-05714-5

Kim, W.-T., Mun, J.-Y., Baek, S.-W., Kim, M.-H., Yang, G.-E., Jeong, M.-S., Choi, S. Y., Han, J.-Y., Kim, M. H., & Leem, S.-H. (2022). Secretory SERPINE1 Expression is Increased by Antiplatelet Therapy, Inducing MMP1 Expression and Increasing Colon Cancer Metastasis. International Journal of Molecular Sciences, 23(17), 9596. https://doi.org/10.3390/ijms23179596

Kováčová, Z., & Hodorová, I. (2021). Carbonic Anhydrase IX and Survivin in Colorectal Adenocarcinoma Cells: Slovakian Population Study. Biology, 10(9), 872. https://doi.org/10.3390/biology10090872

Lai, X., Dong, Q., Xu, F., Wu, S., Yang, D., Liu, C., Li, Y., Li, Z., & Ma, D. (2021). Correlation of c-MET Expression with Clinical Characteristics and the Prognosis of Colorectal Cancer. Journal of Gastrointestinal Oncology, 12(5), 2203–2210. https://doi.org/10.21037/jgo-21-536

Li, C., Wang, Y., Liu, D., Wong, C. C., Coker, O. O., Zhang, X., Liu, C., Zhou, Y., Liu, Y., Kang, W., To, K. F., Sung, J. J., & Yu, J. (2022). Squalene Epoxidase Drives Cancer Cell Proliferation and Promotes Gut Dysbiosis to Accelerate Colorectal Carcinogenesis. Gut, 71(11), 2253–2265. https://doi.org/10.1136/gutjnl-2021-325851

Li, X.-X., Liu, C., Dong, S.-L., Ou, C.-S., Lu, J.-L., Ye, J.-H., Liang, Y.-R., & Zheng, X.-Q. (2022). Anticarcinogenic Potentials of Tea Catechins. Frontiers in Nutrition, 9, 1060783. https://doi.org/10.3389/fnut.2022.1060783

Najaf-Najafi, M., Salehi, M., Ghazanfarpour, M., Hoseini, Z. S., & Khadem-Rezaiyan, M. (2018). The Association Between Green Tea Consumption and Breast Cancer Risk: A Systematic Review and Meta-Analysis. Phytotherapy Research, 32(10), 1855–1864. https://doi.org/10.1002/ptr.6124

Neuhaus, T., Pabst, S., Stier, S., Weber, A.-A., Schrör, K., Sachinidis, A., Vetter, H., & Ko, Y. D. (2004). Inhibition of the Vascular-Endothelial Growth Factor-Induced Intracellular Signaling and Mitogenesis of Human Endothelial Cells by Epigallocatechin-3-Gallate. European Journal of Pharmacology, 483(2–3), 223–227. https://doi.org/10.1016/j.ejphar.2003.10.029

Nikonova, A. S., Astsaturov, I., Serebriiskii, I. G., Dunbrack, R. L., & Golemis, E. A. (2013). Aurora A Kinase (AURKA) in Normal and Pathological Cell Division. Cellular and Molecular Life Sciences, 70(4), 661–687. https://doi.org/10.1007/s00018-012-1073-7

Pastorekova, S., & Gillies, R. J. (2019). The Role of Carbonic Anhydrase IX in Cancer Development: Links to Hypoxia, Acidosis, and Beyond. Cancer and Metastasis Reviews, 38(1–2), 65–77. https://doi.org/10.1007/s10555-019-09799-0

Rovik, A., Andyra, V. U., Afifah, L., & Rokhmalia, N. (2024). Etnobotani dan Potensi Suruhan (Peperomia pellucida) sebagai Bahan Obat Herbal. Journal of Biomedical Sciences and Health, 2(2), 53–66. http://dx.doi.org/10.34310/718g9w21

Shirakami, Y., & Shimizu, M. (2018). Possible Mechanisms of Green Tea and Its Constituents Against Cancer. Molecules, 23(9), 2284. https://doi.org/10.3390/molecules23092284

Suetsugu, T., Mori, R., Futamura, M., Fukada, M., Tanaka, H., Yasufuku, I., Sato, Y., Iwata, Y., Imai, T., Imai, H., Tanaka, Y., Okumura, N., Matsuhashi, N., Takahashi, T., & Yoshida, K. (2021). Mechanism of Acquired 5FU Resistance and Strategy for Overcoming 5FU Resistance Focusing on 5FU Metabolism in Colon Cancer Cell Lines. Oncology Reports, 45(4), 27. https://doi.org/10.3892/or.2021.7978

Susilo, F. E., Surjaputra, I. V., Boentoro, F. A., Ariela, Y., & Sulistyo, B. (2023). Systematic Review of the Anticancer Activity of Green Tea (Camellia sinensis)-Derived Compounds in Breast Cancer in Vitro. Indonesian Journal of Life Sciences, 5(1), 56–77. https://doi.org/10.54250/ijls.v3i2.145

Tang, Y.-L., Li, D.-D., Duan, J.-Y., Sheng, L.-M., & Wang, X. (2023). Resistance to Targeted Therapy in Metastatic Colorectal Cancer: Current Status and New Developments. World Journal of Gastroenterology, 29(6), 926–948. https://doi.org/10.3748/wjg.v29.i6.926

Wang, Y., Wang, J., Gao, J., Ding, M., & Li, H. (2023). The Expression of SERPINE1 in Colon Cancer and Its Regulatory Network and Prognostic Value. BMC Gastroenterology, 23(1), 33. https://doi.org/10.1186/s12876-022-02625-y

World Health Organization. (2023). Colorectal Cancer. https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer

Yang, C. S., Wang, H., Chen, J. X., & Zhang, J. (2014). Effects of Tea Catechins on Cancer Signaling Pathways. The Enzymes, 36, 195–221. https://doi.org/10.1016/B978-0-12-802215-3.00010-0

Yao, J.-F., Li, X.-J., Yan, L.-K., He, S., Zheng, J.-B., Wang, X.-R., Zhou, P.-H., Zhang, L., Wei, G.-B., & Sun, X.-J. (2019). Role of HGF/c-Met in the Treatment of Colorectal Cancer with Liver Metastasis. Journal of Biochemical and Molecular Toxicology, 33(6), e22316. https://doi.org/10.1002/jbt.22316

Yu, S., Zhu, L., Wang, K., Yan, Y., He, J., & Ren, Y. (2019). Green Tea Consumption and Risk of Breast Cancer: A Systematic Review and Updated Meta-Analysis of Case-Control Studies. Medicine, 98(27), e16147. https://doi.org/10.1097/MD.0000000000016147

Downloads

Published

2025-09-08

How to Cite

Rovik, A., & Kusharyati, D. F. (2025). Network Analysis Reveals Tea Catechins as Multi-Target Inhibitors of Colon Adenocarcinoma. JRST (Jurnal Riset Sains Dan Teknologi), 9(2), 177–185. https://doi.org/10.30595/jrst.v9i2.23742

Issue

Section

Research in Computer Science and Informatics Engineering

Similar Articles

You may also start an advanced similarity search for this article.