Cancer Chemo-Preventive Effects of Red Propolis: a System Biology Approach

Document Type : Original paper


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

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

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


Background and objectives: Propolis is a natural product of honey bees that is characterized by therapeutic effects on diverse diseases. To elucidate the molecular mechanism of propolis effects on tumor, protein-protein interaction (PPI) network analysis of proteome data of Hep-2 cells treated with red propolis was conducted. Methods: Cytoscape V 3.9.1 and its plug-ins evaluated the differentially expressed proteins (DEPs) in terms of network construction and the corresponding topological features. Results: The results implied that six hub-bottlenecks including ACTB, GAPDH, HSP90AA1, HSPA8, HSP90AB1, and HSPA5 were present in the PPI network; however, only the last central protein was among DEPs. ClueGO+ CluePedia identified five related biological processes and three action types of their connections. Results refer to anticancer property of red propolis. Conclusion: The proposed crucial proteins and their linked biological processes may represent as key players in the anticancer underlying mechanism of red propolis.


Main Subjects

  • Arjmand B, Zamanian Azodi M, Rezaei Tavirani M, Esmaeili S, Vafaee R. Contradictory effects of 6-shogaol on the human cervical cancer cell line HeLa through network analysis. Res J Pharmacogn. 2022; 9(1): 29–37.
  • Šuran J, Cepanec I, Mašek T, Radić B, Radić S, Tlak Gajger I, Vlainić Propolis extract and its bioactive compounds, from traditional to modern extraction technologies. Molecules. 2021; 26(10): 1–21.
  • Oršolić N, Jazvinšćak Jembrek M. Molecular and cellular mechanisms of propolis and its polyphenolic compounds against cancer. Int J Mol Sci. 2022; 23(18): 1–68.
  • Mohammadzadeh S, Sharriatpanahi M, Hamedi M, Amanzadeh Y, Ebrahimi SES, Ostad SN. Antioxidant power of Iranian propolis extract. Food Chem. 2007; 103(3): 729–733.
  • Watanabe MAE, Amarante MK, Conti BJ, Sforcin JM. Cytotoxic constituents of propolis inducing anticancer effects: a review. J Pharm Pharmacol. 2011; 63(11): 1378–1386.
  • Mirzoeva O, Grishanin R, Calder P. Antimicrobial action of propolis and some of its components: the effects on growth, membrane potential and motility of bacteria. Microbiol Res. 1997; 152(3): 239–246.
  • Jacob A, Parolia A, Pau A, Davamani Amalraj F. The effects of Malaysian propolis and Brazilian red propolis on connective tissue fibroblasts in the wound healing process. BMC Complement Altern Med. 2015; 15(1): 1–10.
  • Koo H, Rosalen PL, Cury JA, Park YK, Bowen WH. Effects of compounds found in propolis on Streptococcus mutans growth and on glucosyltransferase activity. Antimicrob Agents Chemother. 2002; 46(5): 1302–1309.
  • Ayres DC, Marcucci MC, Giorgio S. Effects of Brazilian propolis on Leishmania amazonensis. Mem Inst Oswaldo Cruz. 2007; 102(2): 215–220.
  • Park EH, Kahng JH. Suppressive effects of propolis in rat adjuvant arthritis. Arch Pharm Res. 1999; 22(6): 554–558.
  • Belmehdi O, El Menyiy N, Bouyahya A, El Baaboua A, El Omari N, Gallo M, Montesano D, Naviglio D, Zengin G, Skali Senhaji N, Hing Goh B, Abrini Recent advances in the chemical composition and biological activities of propolis. Food Rev Int. In press.
  • Uddin S, Brooks PR, Tran TD. Chemical characterization, α-Glucosidase, α-amylase and lipase inhibitory properties of the Australian honey bee propolis. Foods. 2022; 11(13): 1–18.
  • Kitamura H. Effects of propolis extract and propolis-derived compounds on obesity and diabetes: knowledge from cellular and animal models. Molecules. 2019; 24(23): 1–53.
  • Elfiky AA. Natural products may interfere with SARS-CoV-2 attachment to the host cell. J Biomol Struct Dyn. 2021; 39(9): 3194–3203.
  • da Silva Frozza CO, da Silva Ribeiro T, Gambato G, Menti C, Moura S, Pinto PM, Christian Staats C, Padilha FF, Rech Begnini K, de Leon PMM, Borsuk S, Savegnago L, Dellagostin O, Collares T, Kömmling Seixas F, Henriques JAP, Roesch-Ely Proteomic analysis identifies differentially expressed proteins after red propolis treatment in Hep-2 cells. Food Chem Toxicol. 2014; 63: 195–204.
  • Smoot ME, Ono K, Ruscheinski J, Wang PL, Ideker T. Cytoscape 2.8: new features for data integration and network visualization. Bioinformatics. 2011; 27(3): 431–432.
  • Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P, Jensen LJ, Mering STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res. 2019; 47(D1): 607–613.
  • Whitt W. The queueing network analyzer. Bell Syst Tech J. 1983; 62(9): 2779–2815.
  • Bindea G, Mlecnik B, Hackl H, Charoentong P, Tosolini M, Kirilovsky A, Fridman WH, Pagès F, Trajanoski Z, Galon ClueGO: a cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics. 2009; 25(8): 1091–1093.
  • Elumalai P, Muninathan N, Megalatha ST, Suresh A, Kumar KS, Jhansi N, Kalaivani K, Krishnamoorthy G. An insight into anticancer effect of propolis and its constituents: a review of molecular mechanisms. Evid Based Complement Alternat Med. 2022; Article ID 5901191.
  • Balc-Okcanoğlu T, Yilma-Susluer S, Kayabasi C, Ozme-Yelken B, Biray-Avci C, Gunduz C. The effect of caffeic acid phenethyl ester on cell cycle control gene expressions in breast cancer cells. Mol Biol Res Commun. 2021; 10(1): 39–43.
  • Gu Y, Tang S, Wang Z, Cai L, Lian H, Shen Y, Zhou A pan-cancer analysis of the prognostic and immunological role of β-actin (ACTB) in human cancers. Bioengineered. 2021; 12(1): 6166–6185.
  • Zhang JY, Zhang F, Hong CQ, Giuliano AE, Cui XJ, Zhou GJ, Zhang GJ, Cui Critical protein GAPDH and its regulatory mechanisms in cancer cells. Cancer Biol Med. 2015; 12(1): 10–22.
  • Forma E, Bryś M. Anticancer activity of Propolis and ats compounds. Nutrients. 2021; 13(8): 1–21.
  • Radovanović V, Vlainić J, Hanžić N, Ukić P, Oršolić N, Baranović G, Jembrek Neurotoxic effect of ethanolic extract of propolis in the presence of copper ions is mediated through enhanced production of ROS and stimulation of caspase-3/7 activity. Toxins. 2019; 11(5): 1–18.
  • Bhattacharyya N, Gupta S, Sharma S, Soni A, Bagabir SA, Bhattacharyya M, Mukherjee A, Almalki AH, Alkhanani MF, Haque S, Kumar Ray A, Malik CDK1 and HSP90AA1 appear as the novel regulatory genes in non-small cell lung cancer: a bioinformatics approach. J Pers Med. 2022; 12(3): 1–18.
  • Bailly C, Vergoten G. Anticancer properties and mechanism of action of oblongifolin C, guttiferone K and related polyprenylated acylphloroglucinols. Nat Prod Bioprospect. 2021; 11(6): 629–641.
  • Shan N, Zhou W, Zhang S, Zhang Y. Identification of HSPA8 as a candidate biomarker for endometrial carcinoma by using iTRAQ-based proteomic analysis. Onco Targets Ther. 2016; 9: 2169–2179.
  • Zagouri F, Sergentanis TN, Gazouli M, Tsigginou A, Dimitrakakis C, Papaspyrou I, Eleutherakis-Papaiakovou E, Chrysikos D, Theodoropoulos G, Zografos GC, Antsaklis A, Dimopoulos AM, Papadimitriou HSP90, HSPA8, HIF-1 alpha and HSP70-2 polymorphisms in breast cancer: a case–control study. Mol Biol Rep. 2012; 39(12): 10873–10879.
  • Minghui W, Lin F, Ping L, Naijun H, Yanning G, Ting X. Hsp90AB1 protein is overexpressed in non-small cell lung cancer tissues and associated with poor prognosis in lung adenocarcinoma patients. Zhongguo Fei Ai Za Zhi. 2016; 19(2): 64–69.
  • Li Z, Chen B, Wang P, Li X, Cai G, Wei W, Dong W. A proteomic analysis of acute leukemia cells treated with 9-hydroxyoctadecadienoic acid. Lipids Health Dis. 2016; 15(1): 1–8.
  • Zhang C, Liu Q, Zhou Y, Hua J, Su R, Ai J. HSPA5 could be a prognostic biomarker correlated with immune infiltration in breast cancer. Disease Markers. 2022; Article ID 7177192.