• Logo
  • SBMUJournals

Investigation of health benefits of cocoa in human colorectal cancer cell line, HT-29 through interactome analysis

Mona Zamanian Azodi, Mostafa Rezaei-Tavirani




Aim: This bioinformatics study aims to identify the potential key genes influenced by cocoa extraction treatment on colon cancer cell line HT-29 after 24h.

Background: Cocoa consumption has been claimed to have a beneficial effect on cancer.

Methods: The microarray dataset (GSE94154) from GEO, was the source for differentially expressed genes (DEGs) extraction through GEO2R analysis. The comparison was between 3 controls of colorectal cell line HT-29 and 3 ones incubated with cocoa extraction after 24 h. Afterwards, the top significant DEGs were assigned for protein-protein interaction network construction and analysis by Cytoscape v 3.7.0. and the related applications.

Results: The findings indicate that there are 222 up-regulated and 28 down-regulated genes among 250 top-ranked DEGs. What is more, centrality analysis of the DEGs network identified 10 hub-bottlenecks that ISG15, MX 1, and STAT1 were among the significant differential expression genes with the contribution in type 1 interferon signaling pathway, positive regulation of erythrocyte differentiation, and negative regulation of viral genome replication.

Conclusion:  In conclusion, the underlying mechanisms of cocoa treatment could be clarified by its up-regulatory and modulatory effect on prominent genes of tumor suppressor family. In other words, valuable clues for future clinical studies of cocoa health benefits are highlighted in this study once validation studies are carried out. 


: Colon cancer, Cocoa extraction, Transcriptome, Interactome profile, Tumor suppressor genes


Buchwald P, Hall C, Davidson C, Dixon L, Dobbs B, Robinson B, et al. Improved survival for rectal cancer compared to colon cancer: the four cohort study. ANZ J Surg 2018;88:E114-7.

Lacy AM, García-Valdecasas JC, Delgado S, Castells A, Taurá P, Piqué JM, et al. Laparoscopy-assisted colectomy versus open colectomy for treatment of non-metastatic colon cancer: a randomised trial. Lancet 2002;359:2224-9.

Dalilan S, Rezaei-Tavirani M, Nabiuni M, Heidari-Keshel S, Azodi MZ, Zali H. Aqueous extract of Lavender angustifolia inhibits lymphocytes proliferation of Hodgkin's lymphoma patients. Iran J Cancer Prev 2013;6:201.

Rezaie-Tavirani M, Fayazfar S, Heydari-Keshel S, Rezaee MB, Zamanian-Azodi M, Rezaei-Tavirani M, et al. Effect of essential oil of Rosa Damascena on human colon cancer cell line SW742. Gastroenterol Hepatol Bed Bench 2013;6:25.

Andújar I, Recio M, Giner R, Ríos J. Cocoa polyphenols and their potential benefits for human health. Oxid Med Cell Longev 2012;2012:906252.

Martínez-Pinilla E, Oñatibia-Astibia A, Franco R. The relevance of theobromine for the beneficial effects of cocoa consumption. Front Pharmacol 2015;6:30.

Corti R, Flammer AJ, Hollenberg NK, Lüscher TF. Cocoa and cardiovascular health. Circulation 2009;119:1433-41.

Llorach R, Urpi-Sarda M, Jauregui O, Monagas M, Andres-Lacueva C. An LC-MS-based metabolomics approach for exploring urinary metabolome modifications after cocoa consumption. J Proteome Res 2009;8:5060-8.

Martín M, Goya L, Ramos S. Preventive effects of cocoa and cocoa antioxidants in colon cancer. Dis 2016;4:6.

Ramljak D, Romanczyk LJ, Metheny-Barlow LJ, Thompson N, Knezevic V, Galperin M, et al. Pentameric procyanidin from Theobroma cacao selectively inhibits growth of human breast cancer cells. Mol Cancer Ther 2005;4:537-46.

Sauceda-Friebe JC, Karsunke XY, Vazac S, Biselli S, Niessner R, Knopp D. Regenerable immuno-biochip for screening ochratoxin A in green coffee extract using an automated microarray chip reader with chemiluminescence detection. Anal Chimi Acta 2011;689:234-42.

Shannon P, Markiel A, Ozier O, Baliga NS, Wang JT, Ramage D, et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Gen Res 2003;13:2498-504.

Fathi F, Oskouie AA, Tafazzoli M, Naderi N, Sohrabzedeh K, Fathi S, et al. Metabonomics based NMR in Crohn's disease applying PLS-DA. Gastroenterol Hepatol Bed Bench. 2013;6:S82-6.

Asadzadeh-Aghdaee H, Shahrokh S, Norouzinia M, Hosseini M, Keramatinia A, Jamalan M, et a

l. Introduction of inflammatory bowel disease biomarkers panel using protein-protein interaction (PPI) network analysis. Gastroenterol Hepatol Bed Bench. 2016;9:S8-S13.

Kacprowski T, Doncheva NT, Albrecht M. Network Prioritizer: a versatile tool for network-based prioritization of candidate disease genes or other molecules. Bioinformatics 2013;29:1471-3.

Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, et al. ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics 2009;25:1091-3.

Zamanian-Azodi M, Rezaei-Tavirani M, Rostami-Nejad M, Tajik-Rostami F. New Molecular Aspects of Cardiac Arrest; Promoting Cardiopulmonary Resuscitation Approaches. Emerg 2018;6:40.

Hu JL, Hua YJ, Chen Y, Yu B, Gao S. Structural analysis of tumor-related single amino acid mutations in human MxA protein. Chin J Cancer 201528;34:583-93.

Mushinski JF, Nguyen P, Stevens LM, Khanna C, Lee S, Chung EJ, et al. Inhibition of tumor cell motility by the interferon-inducible GTPase MxA. J Bio Chem 2009;284:15206-14.

Cajee U-F, Hull R, Ntwasa M. Modification by ubiquitin-like proteins: significance in apoptosis and autophagy pathways. Int journal Mol Sci 2012;13:11804-31.

Yeung TL, Tsai C, Leung C, Au Yeung CL, Thompson M, Lu K, et al. ISG15 promotes ERK1 ISGylation, CD8+ T cell activation and suppresses ovarian cancer progression. Cancer 2018;10:464.

Zuo C, Sheng X, Min Ma MX, Ouyang L. ISG15 in the tumorigenesis and treatment of cancer: An emerging role in malignancies of the digestive system. Oncotarget 2016;7:74393.

Kaler P, Owusu BY, Augenlicht L, Klampfer L. The role of STAT1 for crosstalk between fibroblasts and colon cancer cells. Front Oncol 2014;4:88.

Di Franco S, Turdo A, Todaro M, Stassi G. Role of type I and II interferons in colorectal cancer and melanoma. Front Immunol 2017;8:878.

DOI: https://doi.org/10.22037/ghfbb.v0i0.1557