Evaluation of Anticancer Effect of Ghost Pepper: A Bioinformatics Assessment

Document Type : Original paper


1 Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

2 Proteomics Research Center, Faculty of Paramedical Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

3 Traditional Medicine and Materia Medica Research Center and Department of Traditional Pharmacy, School of Traditional Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

4 Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

5 Laser Application in Medical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.


Background and objectives: Natural sources can be effective in treating diverse pathological conditions especially cancer. Molecular evaluations of pepper on renal cancer could provide further information about its anticancer property. Methods: To achieve a clear understanding of pepper effect on cancer cells, protein-protein interaction network analysis of differentially expressed proteins (DEPs) in human renal adenocarcinoma cells treated with ghost pepper were evaluated. Cytoscape V. 3.8.2 and its applications were applied to analyze the DEPs. Results: Centrality study showed CYCS and CAT as DEPs were the hub-bottlenecks that were essential for the network stability. Among the 10 introduced central proteins, eight individuals belonged to the added first neighbors from STRING database. The finding indicated that the main central proteins belonged to the first neighbors of the queried proteins and were involved in the anticancer activity. Conclusion: Analysis highlighted anticancer property of ghost pepper on the human renal adenocarcinoma cells and also antioxidant effect which was associated with catalase activity.


[1] Irshad S, Ashfaq A, Muazzam A, Yasmeen A. Antimicrobial and anti-prostate cancer activity of turmeric (Curcuma longa L.) and black pepper (Piper nigrum L.) used in typical Pakistani cuisine. Pak J Zool. 2017; 49(5): 1–5.
[2] Clark R, Lee SH. Anticancer properties of capsaicin against human cancer. Anticancer Res. 2016; 36(3): 837–843.
[3] Spiller F, Alves MK, Vieira SM, Carvalho TA, Leite CE, Lunardelli A,  Poloni JA, Cunha FQ, De Oliveira JR. Anti‐inflammatory effects of red pepper (Capsicum baccatum) on carrageenan‐and antigen‐induced inflammation. J Pharm Pharmacol. 2008; 60(4): 473–478.
[4] Lee SC, Hwang IS, Choi HW, Hwang BK. Involvement of the pepper antimicrobial protein CaAMP1 gene in broad spectrum disease resistance. Plant Physiol. 2008; 148(2): 1004–1020.
[5] Renault S, De Lucca A, Boue S, Bland J, Vigo C, Selitrennikoff C. CAY-I, a novel antifungal compound from cayenne pepper. Med Mycol. 2003; 41(1): 75–82.
[6] Kamaruddin MF, Hossain MZ, Mohamed Alabsi A, Mohd Bakri M. The antiproliferative and apoptotic effects of capsaicin on an oral squamous cancer cell line of Asian origin, ORL-48. Medicina. 2019; 55(7): 1–12.
[7] Perla V, Nadimi M, Reddy R, Hankins GR, Nimmakayala P, Harris RT, Valluri J, Sirbu C, Reddy UK. Effect of ghost pepper on cell proliferation, apoptosis, senescence and global proteomic profile in human renal adenocarcinoma cells. PLoS One. 2018; 13(10): 1–27.
[8] Samykutty A, Shetty AV, Dakshinamoorthy G, Bartik MM, Johnson GL, Webb B, Zheng G, Chen A, Kalyanasundaram R, Munirathinam G. Piperine, a bioactive component of pepper spice exerts therapeutic effects on androgen dependent and androgen independent prostate cancer cells. PLoS One. 2013; 8(6): 1–11.
[9] Zhu M, Yu X, Zheng Z, Huang J, Yang X, Shi H. Capsaicin suppressed activity of prostate cancer stem cells by inhibition of Wnt/β‐catenin pathway. Phytother Res. 2020; 34(4): 817–824.
[10] Liu Y, Nair MG. Capsaicinoids in the hottest pepper Bhut Jolokia and its antioxidant and antiinflammatory activities. Nat Prod Commun. 2010; 5(1): 91–94.
[11] Zamanian-Azodi M, Rezaei-Tavirani M. Investigation of health benefits of cocoa in human colorectal cancer cell line, HT-29 through interactome analysis. Gastroenterol Hepatol Bed Bench. 2019; 12(1): 67–73.
[12] Rezaei-Tavirani M, Tavirani MR, Azodi MZ. The bioinformatics aspects of gene screening of HT-29, human colon cell line treated with caffeic acid. Gastroenterol Hepatol Bed Bench. 2019; 12(3): 246–253.
[13] Zamanian-Azodi M, Rezaei-Tavirani M, Nejadi N, Oskouie AA, Zayeri F, Hamdieh M, Safaei A, Rezaei-Tavirani M, Ahmadzadeh A, Amouzandeh-Nobaveh A, Okhovatian F. Serum proteomic profiling of obsessive-compulsive disorder, washing subtype: a preliminary study. Basic Clin Neurosci. 2017; 8(4): 307–316.
[14] Azodi MZ, Rezaei-Tavirani M, Rezaei-Tavirani M. Identification of the key genes of autism spectrum disorder through protein-protein interaction network. Galen Med J. 2019; 8: 1–8.
[15] Zali MR, Azodi MZ, Razzaghi Z, Heydari MH. Gallbladder cancer integrated bioinformatics analysis of protein profile data. Gastroenterol Hepatol Bed Bench. 2019; 12(Suppl1): 66–73.
[16] Smoot ME, Ono K, Ruscheinski J, Wang PL, Ideker T. Cytoscape 2.8: new features for data integration and network visualization. Bioinform. 2011; 27(3): 431–432.
[17] Szklarczyk D, Morris JH, Cook H, Kuhn M, Wyder S, Simonovic M, Alberto Santos A, Doncheva NT, Roth A, Bork P, Jensen LJ, Von Mering C. The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible. Nucleic Acids Res. 2016: 45(1): 362–368.
[18] Assenov Y, Ramírez F, Schelhorn SE, Lengauer T, Albrecht M. Computing topological parameters of biological networks. Bioinform. 2008; 24(2): 282–284.
[19] Heidari MH, Razzaghi M, Baghban AA, Rostami-Nejad M, Rezaei-Tavirani M, Azodi MZ, Zali A, Ahmadzadeh A. Assessment of the microbiome role in skin protection against uv irradiation via network analysis. J Lasers Med Sci. 2020; 11(3): 238–242.
[20] Bindea G, Galon J, Mlecnik B. CluePedia cytoscape plugin: pathway insights using integrated experimental and in silico data. Bioinform. 2013; 29(5): 661–663.
[21] Mukherjee AK, Basu S, Sarkar N, Ghosh AC. Advances in cancer therapy with plant based natural products. Curr Med Chem. 2001; 8(12): 1467–1486.
[22] Ulz P, Heitzer E, Speicher MR. Co-occurrence of MYC amplification and TP53 mutations in human cancer. Nat Genet. 2016; 48(2): 104–106.
[23] Azodi MZ, Peyvandi H, Rostami-Nejad M, Safaei A, Rostami K, Vafaee R, Heidari M, Hosseini M, Zali MR. Protein-protein interaction network of celiac disease. Gastroenterol Hepatol Bed Bench. 2016; 9(4): 268–277.
[24] Yin X, Yu J, Zhou Y, Wang C, Jiao Z, Qian Z, Sun H, Chen B. Identification of CDK2 as a novel target in treatment of prostate cancer. Future Oncol. 2018; 14(8): 709–718.
[25] Shay JW, Bacchetti S. A survey of telomerase activity in human cancer. Eur J Cancer. 1997; 33(5): 787–791.
[26] Sorensen CS, Lukas C, Kramer ER, Peters JM, Bartek J, Lukas J. A conserved cyclin-binding domain determines functional interplay between anaphase-promoting complex–Cdh1 and cyclin A-Cdk2 during cell cycle progression. Mol Cell Biol. 2001; 21(11): 3692–3703.
[27] Kirkman HN, Gaetani GF. Mammalian catalase: a venerable enzyme with new mysteries. Trends Biochem Sci. 2007; 32(1): 44–50.
[28] Halliwell B, Clement MV, Long LH. Hydrogen peroxide in the human body. FEBS Lett. 2000; 486(1): 10–13.
[29] Góth L, Rass P, Páy A. Catalase enzyme mutations and their association with diseases. Mol Diagn. 2004; 8(3): 141–149.