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.
Matthew J walsh Je, and Guillaume M Hautbergue. Ribosome-inactivating proteins: Potent poisons and molecular tools. Virulence. 2013;4(8):774–84.
Roger Gilabert-Oriol AW, Benedicta von Mallinckrodt, Matthias F. Melzig, Hendrik Fuchs, and Mayank Thakur. Immunotoxins Constructed with Ribosome-Inactivating Proteins and their Enhancers: A Lethal Cocktail with Tumor Specific Efficacy. Current Pharmaceutical Design. 2014;20:6584-643.
Joachim Schrot AWaMFM. Ribosome-Inactivating and Related Proteins. Toxins. 2015;7:1556-615.
T.B. Ng JHWaHW. Recent Progress in Research on Ribosome Inactivating Proteins. Current Protein and Peptide Science. 2010;11:37-53.
Anna Falasca AG-C, Ada Abbondanza, Luigi Barbieri and Fiorenzo Stirpe. Properties of the ribosome-inactivating proteins gelonin, Momordica charantia inhibitor, and dianthins. Biochem J 1982;207:505-9.
Willy J. Peumans QH aEJMVD. Ribosome-inactivating proteins from plants: more than RNA N-glycosidases? The FASEB Journal. 2001;15:1493-506.
Battelli FSaMG. Ribosome-inactivating proteins: progress and problems. Cellular and Molecular Life Sciences CMLS. 2006;63(16):1850-66.
Lucía Citores RIaJMF. 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.
Libério MS1 JG, Fontes W, Castro MS. Anticancer peptides and proteins: a panoramic view. Protein Pept Lett. 2013;20(4):380-91.
Fiorenzo Stirpe DGW, Lesley J. Onyon and Robert F. Legg. Dianthins, ribosome-damaging proteins with anti-viral properties from Dianthus caryophyllus L. Biochem. 1981;195:399-405.
https://www.dojindo.com/Protocol/Cell_Proliferation_Protocol_Colorimetric.pdf. Measuring Cell Viability / Cytotoxicity.1-12.
Noel J Leigh RIL, Pamela A Hershberger, Maciej L Goniewicz. lavourings significantly affect inhalation toxicity of aerosol generated from electronic nicotine delivery systems (ENDS). Tob Control. 2016;25:ii81–ii7.
Banáth PLOaJP. The comet assay: a method to measure DNA damage in individual cells. Nature Protocols. 2006;1(1):23-9.
Organization WH. 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. 2018:1-3.
MohammadEsmaeil Akbari SS, Saed Sayad, Maryam Khayamzadeh, Leila Shojaee, Zeynab Shormeji, and Mojtaba Amiri. Breast Cancer Status in Iran: Statistical Analysis of 3010 Cases between 1998 and 2014. International Journal of Breast Cancer. 2017;2:10.
Andrea Bolognesi PLT, Giuseppe Legname, Fabiola Olivieri, Daniela Modena, Roberto Conte, Fiorenzo Stirpe Anti-CD30 immunotoxins with native and recombinant dianthin 30. Cancer Immunol Immunother. 1995;40:109-14.
Irene Lorenzetti AM, Giulio Fracasso, Cristina Potrich, Laura Costantini, Elena Chiesa, Giuseppe Legname, Gianfranco Menestrina, Giuseppe Tridente And Marco Colombatti. 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. Int J Cancer. 2000;86:582–9.
Cheenu Bhargava HD, Xiangli Zhao, Alexander Weng, Matthias F. Melzig, and Hendrik Fuchs. Targeted dianthin is a powerful toxin to treat pancreatic carcinoma when applied in combination with the glycosylated triterpene SO1861. Molecular Oncology. 2017;11:1527–43.
Evandro Fei Fang CZYZ, Lin Zhang, Jack Ho Wong, Yau Sang Chan, Wen Liang Pan, Xiu Li Dan, Cui Ming Yin, Chi Hin Cho, Tzi Bun Ng. Trichosanthin inhibits breast cancer cell proliferation in both cell lines and nude mice by promotion of apoptosis. Plos One. 2012;7(9):1-11.
Hong Zhou WNH, Hideo Yagita, Lawrence H. Cheung, Stuart S. Martin, Jeffrey A. Winkles, and Michael G. Rosenblum. Antitumor activity of a humanized, bivalent immunotoxin targeting fn14-positive solid tumors. Cancer Res. 2013;73(14):4439–50.
Pan WL1 WJ, 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. Biochim Biophys Acta. 2013;1833(5):987-96.
Deng NH WL, He QC, Zheng JC, Meng Y, Meng YF, Zhang CJ, Shen FB. Pegylation alleviates the non-specific toxicities of Alpha-Momorcharin and preserves its antitumor efficacy in vivo. Drug Deliv. 2016;23(1):95-100.
Qiu HI RJ, Ding XZ, Hu SB, Zhang YM, Zhu DQ, et al. Prokaryotic expression of MAP30 from Momordica charantia and its biological activity. China Biotechnol. 2014;34:40-6.
Adwan H BH, Pervaiz A, Sagini M, Berger MR. Riproximin is a recently discovered type II ribosome inactivating protein with potential for treating cancer. Biotechnol Adv. 2014;32(6):1077-90.
Turnay J ON, 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. Mol Cell Biochem. 1993;122(1):39-47.
Liu L WR, He W, He F, Huang G. Cloning and soluble expression of mature alpha-luffin from Luffa cylindrica and its antitumor activities in vitro. Acta Biochim Biophys Sin (Shanghai). 2010;42(8):585-92.
Z H. Impact of impurities on IC50 values of P450 inhibitors. Drug Metab Lett. 2011;5(3):156-62.