• Logo
  • SBMUJournals

Introduction of Dianthins: A New Promising Horizon Toward Continuous Research on Breast Cancer Bulldozing in Iran

Mohammad Hossein pour, Jamil Zargan, Hossein Honari, Ashkan Haji Nour Mohammadi, Abbas Hajizadeh, Hani Keshavarz Alikhani, Ahmad Heidari, Ehsan Zamani




Background: The production and secretion of defense proteins are one of the protective mechanisms exploited by plants against pathogens. The production and secretion of defense proteins are one of the protective mechanisms exploited by plants against pathogens. Ribosome-Inactivating Proteins (RIPs), as the main class of these proteins, are considered to facilitate cancer therapy worldwide, because of the potential anticancer activity. Indeed, some of these proteins have cytotoxic and anticancer properties. Extracted from the carnation (Dianthus caryophyllus), Dianthin inhibits protein synthesis in many different cells.
Methods: In this research, the Dianthins was isolated and purified from the leaves of D. caryophyllus, using ion-exchange chromatography column (CM-Sephadex G-50). Subsequently, its cytotoxicity effect on MCF-7 cell line was investigated. The cell cytotoxicity assessment was performed, using 3-(4,5-Dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT), neutral red uptake, and alkaline comet assays at the concentrations of 1.25μg/mL to 10μg/mL of the protein applying the MCF-7 cell line.
Results: the toxin induces cell death, mostly via necrosis rather than apoptosis, but in the special range of concentrations.
Conclusion: because of the severe side effects of chemotherapy drugs, this toxin can undergo more research as a new drug candidate against breast cancer.


Dianthin, Dianthus caryophyllus, MTT assay, Neutral red uptake assay, MCF-7


Walsh MJ, Dodd JE, Hautbergue GM. Ribosome-inactivating proteins: Potent poisons and molecular tools. Virulence. 2013; 4(8):774-84. [DOI:10.4161/viru.26399] [PMID] [PMCID]

Gilabert-Oriol R, Weng A, Mallinckrodt Bv, Melzig MF, Fuchs H, Thakur M. Immunotoxins constructed with ribosome-inactivating proteins and their enhancers: A Lethal cocktail with tumor specific efficacy. Current Pharmaceutical Design. 2014; 20(42):6584-643. [DOI:10.2174/1381612820666140826153913] [PMID] [PMCID]

Schrot J, Weng A, Melzig MF. Ribosome-inactivating and related proteins. Toxins. 2015; 7(5):1556-615. [DOI:10.3390/toxins7051556] [PMID] [PMCID]

Ng TB, Wong JH, Wang H. Recent progress in research on ribosome inactivating proteins. Current Protein and Peptide Science. 2010; 11(1):37-53. [DOI:10.2174/138920310790274662]

Falasca A, Gasperi-Campani A, Abbondanza A, Barbieri L, Stirpe F. Properties of the ribosome-inactivating proteins gelonin, momordica charantia inhibitor, and dianthins. Biochemical Journal. 1982; 207(3):505-9. [DOI:10.1042/bj2070505] [PMID] [PMCID]

Peumans WJ, Hao Q, Van Damme EJ. Ribosome-inactivating proteins from plants: More than RNA N-glycosidases? The FASEB Journal. 2001; 15(9):1493-506. [DOI:10.1096/fj.00-0751rev] [PMID]

Stirpe F, Battelli MG. Ribosome-inactivating proteins: Progress and problems. Cellular and Molecular Life Sciences. 2006; 63(16):1850-66. [DOI:10.1007/s00018-006-6078-7] [PMID]

Citores L, Iglesias R, Ferreras JM. Ribosome inactivating proteins from plants: biological properties and their use in experimental therapy. Antitumor Potential and other Emerging Medicinal Properties of Natural Compounds. 2013:127-43. [DOI:10.1007/978-94-007-6214-5_9]

Liberio MS, Joanitti GA, Fontes W, Castro MS. Anticancer peptides and proteins: A panoramic view. Protein and Peptide Letters. 2013; 20(4):380-91. [DOI:10.2174/092986613805290435]

Stirpe F, Williams DG, Onyon LJ, Legg RF, Stevens WA. Dianthins, ribosome-damaging proteins with anti-viral properties from Dianthus caryophyllus L. (carnation). Biochemistry. 1981; 195(2):399-405. [DOI:10.1042/bj1950399] [PMID] [PMCID]

Dojindo Molecular Technologies, Inc. Cell proliferation protocol colorimetric [Internet] 2019 [Retrieved 2019 August 25]. Available from: https://www.dojindo.com/Protocol/Cell_Proliferation_Protocol_Colorimetric.pdf

Leigh NJ, Lawton RI, Hershberger PA, Goniewicz ML. Flavourings significantly affect inhalation toxicity of aerosol generated from electronic nicotine delivery systems (ENDS). Tobacco Control. 2016; 25(suppl. 2):ii81-7. [DOI:10.1136/tobaccocontrol-2016-053205] [PMID] [PMCID]

Olive PL, Banáth JP. The comet assay: A method to measure DNA damage in individual cells. Nature Protocols. 2006; 1(1):23-9. [DOI:10.1038/nprot.2006.5] [PMID]

World Health Organization. Latest global cancer data: Cancer burden rises to 18.1 million new cases and 9.6 million cancer deaths in 2018. International Agency for Research on Cancer. Geneva: World Health Organization; 2018.

Akbari ME, Sayad S, Sayad S, Khayamzadeh M, Shojaee L, Shormeji Z, et al. Breast cancer status in Iran: Statistical analysis of 3010 cases between 1998 and 2014. International Journal of Breast Cancer. 2017; 2017:2481021. [DOI:10.1155/2017/2481021] [PMID] [PMCID]

Bolognesi A, Tazzari PL, Legname G, Olivieri F, Modena D, Conte R, Stirpe F. Anti-CD30 immunotoxins with native and recombinant dianthin 30. Cancer Immunology, Immunotherapy. 1995; 40(2):109-14. [DOI:10.1007/BF01520292] [PMID]

Lorenzetti I, Meneguzzi A, Fracasso G, Potrich C, Costantini L, Chiesa E, et al. Genetic grafting of membrane-acting peptides to the cytotoxin dianthin augments its ability to de-stabilize lipid bilayers and enhances its cytotoxic potential as the component of transferrin-toxin conjugates. International Journal of Cancer. 2000; 86(4):582-9. [DOI:10.1002/(SICI)1097-0215(20000515)86:43.0.CO;2-I]

Bhargava C, Dürkop H, Zhao X, Weng A, Melzig MF, Fuchs H. Targeted dianthin is a powerful toxin to treat pancreatic carcinoma when applied in combination with the glycosylated triterpene SO1861. Molecular Oncology. 2017; 11(11):1527-43. [DOI:10.1002/1878-0261.12115] [PMID] [PMCID]

Fang EF, Zhang CZ, Zhang L, Wong JH, Chan YS, Pan WL, et al. Trichosanthin inhibits breast cancer cell proliferation in both cell lines and nude mice by promotion of apoptosis. PLOS One. 2012; 7(9):e41592. [DOI:10.1371/journal.pone.0041592] [PMID] [PMCID]

Zhou H, Hittelman WN, Yagita H, Cheung LH, Martin SS, Winkles JA, et al. Antitumor activity of a humanized, bivalent immunotoxin targeting fn14-positive solid tumors. Cancer Research. 2013; 73(14):4439-50. [DOI:10.1158/0008-5472.CAN-13-0187] [PMID] [PMCID]

Pan WL, Wong JH, Fang EF, Chan YS, Ye XJ, Ng TB. Differential inhibitory potencies and mechanisms of the type I ribosome inactivating protein marmorin on estrogen receptor (ER)-positive and ER-negative breast cancer cells. Biochimica et Biophysica Acta. 2013; 1833(5):987-96. [DOI:10.1016/j.bbamcr.2012.12.013] [PMID]

Deng NH1, Wang L, He QC, Zheng JC, Meng Y, Meng YF, et al. PEGylation alleviates the non-specific toxicities of Alpha-Momorcharin and preserves its antitumor efficacy in vivo. Drug Delivery. 2016; 23(1):95-100. [DOI:10.3109/10717544.2014.905652] [PMID]

Hua-li Q, Jie R, Xue-zhi D, Sheng-biao H, You-ming Z, Dao-qiZ, et al. Prokaryotic expression of MAP30 from Momordica charantia and its biological activity. China Biotechnology. 2014; 34(6):40-6. [DOI:10.13523/j.cb.20140606]

Adwan H, Bayer H, Pervaiz A, Sagini M, Berger MR. Riproximin is a recently discovered type II ribosome inactivating protein with potential for treating cancer. Biotechnology Advances. 2014; 32(6):1077-90. [DOI:10.1016/j.biotechadv.2014.03.008] [PMID]

Turnay J, Olmo N, Jiménez A, Lizarbe MA, Gavilanes JG. Kinetic study of the cytotoxic effect of alpha-sarcin, a ribosome inactivating protein from Aspergillus giganteus, on tumour cell lines: Protein biosynthesis inhibition and cell binding. Molecular and Cellular Biochemistry. 1993; 122(1):39-47. [DOI:10.1007/BF00925735] [PMID]

Liu L, Wang R, He W, He F, Huang G. Cloning and soluble expression of mature alpha-luffin from Luffa cylindrica and its antitumor activities in vitro. Acta Biochimica et Biophysica Sinica (Shanghai). 2010; 42(8):585-92. [DOI:10.1093/abbs/gmq056] [PMID]

Huang Z. Impact of impurities on IC50 values of P450 inhibitors. Drug Metabolism Letters. 2011; 5(3):156-62. [DOI:10.2174/187231211796905008]

DOI: https://doi.org/10.32598/ijmtfm.v9i3.25706