Molecular Docking for Evaluation of Piperine Affinity to the Colon Cancer Receptor
Piperine is an alkaloid found in the plants of the Piperaceae family, such as Piper nigrum and Piper retrofractum. These two plants are commonly used as flavoring agents in daily meals. The piperine extract is reported to be effective in inhibiting the growth of colon cancer cells in laboratory experiments. Between 35-77% of colon cancer cases are caused by excessive expression of the epidermal growth factor receptor. In developing a new compound for commercial drugs, a study of the compound affinity to the receptor is necessary. Hence, the purpose of this study was to comprehensively evaluate the affinity of piperine to the colon cancer receptor using molecular docking software. The AutoDock software was used as a tool for the analysis. Three compounds were analyzed, i.e., the tested ligand (piperine), a native ligand (N-acetyl-D-glucosamine), and a positive control ligand (Gefitinib). Further, the binding score of piperine to the receptor was compared to the binding score of native ligands and positive control ligands. The binding score of the three compounds was found to be -3.82 kcal/mole (piperine), -4.16 kcal/mole (Gefitinib), and -3.75 kcal/mole (N-acetyl-D-glucosamine). It can therefore be concluded that there is a similar affinity between piperine and the control ligand. Therefore, piperine can be recommended and developed as a new drug for colon cancer treatment.
Keywords: piperine, in silico, colon cancer, molecular docking
 Siegel RL, Miller KD, Jemal A. Cancer Statistics, 2017. CA: A Cancer Journal for Clinicians. 2017;67(1):7–30.
 Wilding A, Ingham SL, Lalloo F, et al. Life expectancy in hereditary cancer predisposing diseases: an observational study. Journal of Medical Genetics. 2012;49(4):264–269.
 Wu M, Zhang ZF, Kampman E, et al. Does family history of cancer modify the effects of lifestyle risk factors on esophageal cancer? A population-based case-control study in China. International Journal of Cancer. 2011;128:2147–2157.
 Dahham SS, Majid AM. The impact of life style and nutritional components in primary prevention of colorectal cancer. Journal of Applied Pharmaceutical Science. 2016;6(9):237–244.
 Ministry of Health of Indonesia. Situasi penyakit kanker. 2015.
 Vasavirama K. Piperine: A valuable alkaloid from piper species. International Journal of Pharmacy and Pharmaceutical Sciences. 2014;6(4):34–38.
 Kumar S, Singhal V, Roshan R, Sharma A, Rembhotkar GW, Ghosh B. Piperine inhibits TNF-α induced adhesion of neutrophils to endothelial monolayer through suppression of NF-kappaB and IkappaB kinase activation. European Journal of Pharmacology. 2007;575(1–3):177–186.
 Srinivasan K. Black pepper and its pungent principle-piperine: A review of diverse physiological effects. Critical Reviews in Food Science and Nutrition. 2007;47(8):735–748.
 Yaffe PB, Power Coombs MR, Doucette CD, Walsh M, Hoskin DW. Piperine, an alkaloid from black pepper, inhibits growth of human colon cancer cells via G1 arrest and apoptosis triggered by endoplasmic reticulum stress. Molecular Carcinogenesis. 2015;54(10):1070–1085.
 Kim EJ, Park H, Shin M, Shin HK, Yoon Park JH. Induction of apoptosis in HT-29 human colon cancer cells by the pepper component piperine. Journal of the Korean Society of Food Science and Nutrition. 2009;38(4):442–450.
 Baselga J. Why the epidermal growth factor receptor? The rationale for cancer therapy. The Oncologist. 2002;7(S4 Suppl 4):2–8.
 Jorissen RN, Walker F, Pouliot N, Garrett TP, Ward CW, Burgess AW. Epidermal growth factor receptor: Mechanisms of activation and signalling. Experimental Cell Research. 2003;284(1):31–53.
 Rifaioglu AS, Atas H, Martin MJ, Cetin-Atalay R, Atalay V, Doğan T. Recent applications of deep learning and machine intelligence on in silico drug discovery: Methods, tools and databases. Briefings in Bioinformatics. 2019;20(5):1878–1912.
 Brogi S, Ramalho TC, Kuca K, Medina-Franco JL, Valko M. Editorial: In silico methods for drug design and discovery. Frontiers in Chemistry. 2020;8:612.
 Liu Z, Fang H, Reagan K, Xu X, Mendrick DL, Slikker W Jr, et al. In silico drug repositioning: What we need to know. Drug Discovery Today. 2013;18(3–4):110–115.
 Wang R, Lai L, Wang S. Further development and validation of empirical scoring functions for structure-based binding affinity prediction. Journal of Computer-Aided Molecular Design. 2002;16(1):11–26.
 Velec HF, Gohlke H, Klebe G. DrugScore(CSD)-knowledge-based scoring function derived from small molecule crystal data with superior recognition rate of nearnative ligand poses and better. affinity prediction. Journal of Medicinal Chemistry. 2005;48:6296–6303.
 Krasinskas AM. EGFR signaling in colorectal carcinoma. Pathology Research International. 2011;2011:932932.
 Bouché O, Beretta GD, Alfonso PG, Geissler M. The role of anti-epidermal growth factor receptor monoclonal antibody monotherapy in the treatment of metastatic colorectal cancer. Cancer Treatment Reviews. 2010;36(1):2010.
 Mahipal A, Kothari N, Gupta S. Epidermal growth factor receptor inhibitors: Coming of age. Cancer Control. 2014;21(1):74–79.