ریبونوکلئازها به عنوان عوامل درمانی بالقوه

نوع مقاله : مقاله پژوهشی

نویسندگان

1 گروه علوم دامی، دانشکده کشاورزی، دانشگاه فردوسی مشهد، مشهد، ایران

2 دانشگاه فردوسی مشهد

3 گروه علوم دامی، دانشکده کشاورزی، دانشگاه گیلان، رشت، ایران

4 گروه علوم دامی-دانشکده کشاورزی-دانشگاه فردوسی مشهد-مشهد-ایران

چکیده

هدف: ریبونوکلئازها به دلیل ایجاد سمیت سلولی به عنوان عوامل دارویی دارای پتانسیل درمانی شناخته می­شوند. عملکرد بالای این آنزیم­ها در تخریب رشته RNA و سایر سوبستراهای آن­ها و به دنبال آن انهدام سلول و یا توقف تقسیم سلولی باعث بروز اثر سمیت سلولی بسیار بالای آنزیم­های مذکور در سلول­های سرطانی مختلف می­شود. از این رو در مقاله حاضر  به بررسی کاربردهای درمانی ریبونوکلئازها، مسیرهای سلولی و مکانیسم عمل آن­ها به عنوان عوامل سیتوتوکسیک به منظور توجه به آن­ها در پژوهش­های حوزه سلامت و درمان پرداخته شده است.
مواد و روش‌ها: در این مطالعه با استفاده از کلید واژه­های سرطان، ریبونوکلئاز، مهارکننده ریبونوکلئازی و اسید ریبونوکلئیک، در پایگاه­های اطلاعاتی معتبر Scopus، SID، IranDoc، PubMed، Google Scholar، Web of Science و IranMedex جستجو انجام شد. به منظور انتخاب مستندات مورد استفاده، تمام مقالاتی که به زبان غیرانگلیسی و فارسی چاپ شده بودند، مقالات تکراری، مقالاتی که امکان دستیابی به متن کامل مقاله وجود نداشت و هم­چنین مقالاتی که به صورت چکیده ارائه شده بودند حذف گردیدند. نهایتا موارد منتخب به منظور تنظیم مقاله حاضر به طور کامل مطالعه و خلاصه­سازی شدند.
نتایج: مطالعه و بررسی پژوهش­های انجام شده نشان داد که ریبونوکلئازها توانایی از بین بردن سلول­های تومور را دارا بوده و این آنزیم­ها خصوصیات ضد ویروسی نیز دارند. از میان این آنزیم­ها ریبونوکلئاز پانکراس گاوی، ریبونوکلئاز سمینال گاوی، آنکوناز و انژیوژنین به عنوان ریبونوکلئازهای با فعالیت آنتی­توموری بالا شناخته شده­اند که از طریق مسیرهای مختلف سلولی یا ایجاد جهش در جهت افزایش سمیت سلولی فعالیت سیتوتوکسیتی را علیه سلول­های سرطانی به­صورت انتخابی بروز می­دهند. هم­چنین مطالعه مقالات مرتبط با عملکرد ریبونوکلئازها نشان داد که بررسی مسیرهای ژنتیکی سنتز و مکانیسم­های ایجاد سمیت سلولی در این آنزیم­ها، امکان ایجاد محصولات دارویی جدید را در آینده فراهم خواهد کرد. بهره­گیری از فرآیندهای مهندسی و تغییرات شیمیایی در ساختار لیگاند/رسپتور ممکن است سبب افزایش سمیت مولکول­های ریبونوکلئاز به منظور انتخاب مسیرهای سیتوتوکسیک برای کار بر روی سلول­های بدخیم شود. بنابراین کشف پتانسیل درمانی و بررسی جزییات ارزش­های درمانی ریبونوکلئازها ضروری می­باشد.
نتیجه‌گیری: ریبونوکلئازها کاندیدهای دارویی بالقوه با زیست فراهمی کافی هستند و با توجه به اثر سمیت آن­ها، که بر پایه هیدرولیز انتخابی مولکول­های RNA داخل سلولی و فرآیندهای خاص شناسایی غشاء سلولی می­باشد، می­توان از این آنزیم­ها به­عنوان داروهای ضد تومور و یا عوامل درمانی استفاده کرد.

کلیدواژه‌ها


عنوان مقاله [English]

Ribonucleases as potential therapeutic agents

نویسندگان [English]

  • Masoume Vakili-Azghandi 1
  • mohammadreza nasiri 2
  • Shahrokh Ghovvati 3
  • Ali Javadmanesh 4
1 Animal Science Department, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran
2 ferdosi university of mashhad
3 Animal Science Department, Faculty of Agriculture, University of Guilan, Rasht, Iran
4 Department of Animal Science, Faculty of Agriculture, Ferdowsi University of Mashhad, Mashhad, Iran
چکیده [English]

 
Objective
Due to high cytotoxicity effect, ribonucleases (RNases) are known as pharmacological agents with therapeutic potential. The high potential of these enzymes in the destruction of RNA strand and their other substrates and subsequently, cell destruction or cessation of cell division causes a very high cytotoxic effect of this enzyme in various cancer cells. Hence, this review investigates the therapeutic applications of ribonucleases, cell pathways and their mode of action as cytotoxic agents in order to pay attention to them in researches related to the health and therapy fields.
Materials and methods
In this study the keywords such as cancer, ribonuclease, ribonuclease inhibitor and RNA were used to search in databases including Scopus, SID, IranDoc, PubMed, Google Scholar, Web of Science and IranMedex. In order to select the documents used, all articles published in non-English and Persian languages, duplicate articles, articles that could not be accessed to the full text, as well as articles that were presented as abstracts were removed. Finally, the selected cases were thoroughly studied and summarized in order to prepare the current review.
Results
The study and review of research conducted showed that ribonucleases have the ability to kill tumor cells and that these enzymes have antiviral properties. Bovine pancreatic ribonuclease (RNase A), bovine seminal ribonuclease (BS-RNase), Onconase, and angiogenin are known as RNases with high antitumor activity which exert cytotoxic activity on cancer cells selectively by involving different cellular pathways and/ or enhance the cytotoxicity by mutation. Also, the study of articles related to the function of ribonucleases showed that the investigation of genetic pathways of synthesis and mechanisms of cytotoxicity in these enzymes will provide the development of new pharmaceutical products in the future. Utilization of engineering processes and chemical changes in ligand / receptor structure may increase the toxicity of ribonuclease molecules in order to select cytotoxic pathways on malignant cells. Therefore, it is necessary to discover the therapeutic potential and to study in detail the therapeutic values of ribonucleases.
Conclusions
Ribonucleases are potentially bioavailable drug candidates, and in regard to their toxicity, which is based on the selective hydrolysis of intracellular RNA molecules and specific cell membrane recognition processes, these enzymes can be used as anti-tumor drugs or therapeutic agents.

کلیدواژه‌ها [English]

  • Ribonuclease
  • cytotoxicity
  • drug candidate
  • cellular pathways
آرین­نژاد حمید، نصیری محمدرضا، جوادمنش علی، قوتی شاهرخ، دهقانی حسام، آسوده احمد (1398) طراحی ساختار پروتئینی آنزیم رانپیرناز به عنوان ایمنوتوکسین براساس ریبونوکلئاز پانکراتیک گاوی با استفاده از مطالعات دینامیک و استاتیک مولکولی. پژوهش­های علوم دامی ایران 12، 351-360.
References
Akbari B, Farajnia S, Ahdi Khosroshahi S, Safari F et al. (2017) Immunotoxins in cancer therapy: Review and update. Int Rev Immunol 36, 207-219.
Ardelt W, Ardelt B, Darzynkiewicz Z (2009) Ribonucleases as potential modalities in anticancer therapy. Eur J Pharmacol 625, 181–189.
Ardelt B, Ardelt W, Pozarowski P (2007) Cytostatic and cytotoxic Properties of amphinase: A novel cytotoxic ribonuclease from Rana pipiens oocytes. Cell Cycle 6, 3097-3102.
Ariannejad H, Nassiri MR, Javadmanesh A, Ghovvati S et al. (2019) Designing of protein structural of Ranpirnase based on bovine pancreatic ribonuclease with using molecular dynamic and static simulation. Iranian J Anim Sci Res 12, 351-360 (In Persian).
Arnold U, Ulbrich HR (2006) Natural and engineered ribonucleases as potential cancer therapeutics. Biotechnol Lett 28, 1615-1622.
Baranzini N, De Vito A, Orlandi VT, Reguzzoni M et al. (2020) Antimicrobial role of RNASET2 protein during innate immune response in the medicinal leech hirudo verbana. Front Immunol 11, 370.
Benito A, Ribo M, Vilanova M (2005) On the track of antitumour ribonucleases. Mol BioSyst 1, 294-302.
Boix E, Acquati F, Leonidas D, Pulido D (2020) Editorial: Role of Ribonucleases in immune response regulation during infection and cancer. Front Immunol 11, 236.
Bosch M, Benito A, Ribo M (2004) A nuclear localization sequence endows human pancreatic ribonuclease with cytotoxic activity. Biochem 24, 2167-2177.
Bracale A, Castaldi F, Nitsch L, D’Alessio G (2003) A role for the intersubunit disulfides of seminal RNase in the mechanism of its antitumor action. Eur J Biochm 270, 1980-1987.
Burnysheva KM, Petrushanko IY, Spirin PV (2016) Ribonuclease binase induces death in T-cell acute lymphoblastic leukemia cells by apoptosis. Mol Biol 50, 302-306.
Cruz E, Kayser V (2019) Monoclonal antibody therapy of solid tumors: clinical limitations and novel strategies to enhance treatment efficacy. Biologics 13, 33-51.
Cuchillo CM, Nogués MV, Raines RT (2011) Bovine pancreatic ribonuclease: fifty years of the first enzymatic reaction mechanism. Biochemistry 50, 7835-7841.
Danishefsky SJ, Shue YK, Chang MN, Wong CH (2014) Development of Globo‑H cancer vaccine. ACC Chem Res 48, 643-652.
De Lorenzo C, Arciello A, Cozzolino R, Palmer DB et al. (2004) A fully human antitumor immunoRNase selective for ErbB-2-positive carcinomas. Cancer Res 64, 4870-4874.
Dickson KA, Haigis MC, Raines RT (2005) Ribonuclease inhibitor: Structure and function. Prog Nucleic Acid Res Mol Biol 80, 349–374.
Eller CH, Chao TY, Singarapu KK, Ouerfelli O (2015) Human cancer antigen Globo H is a cell-surface ligand for human Ribonuclease 1. ACS Cent Sci 1,181-190.
Esposito L, Donnarumma F, Ruggiero A, Leone S et al. (2019) Structure, stability and aggregation propensity of a Ribonuclease A-Onconase chimera. Int J Biol Macromol 133, 1125-1133.
Findlay D, Herries DG, Mathias AP, Rabin BR et al. (1961) The active site and mechanism of action of bovine pancreatic ribonuclease. Nature 190, 781–784.
Formoso E, Matxain JM, Lopez X (2010) Molecular dynamics simulation of bovine pancreatic ribonuclease A - CpA and transition state-like complexes. J Phys Chem 114, 7371–7382.
Forouharmehr A, Nassiri MR, Ghovvati Roudsari S, Javadmanesh A (2020) Production and introduction of a novel immunotoxin based on engineered RNase A for inducing death to Her1-positive cell lines. J Cell Physio 235, 4679-4687.
Ghosh SC, Neslihan Alpay S, Klostergaard J (2012) CD44: A validated target for improved delivery of cancer therapeutics. Expert Opin Ther Targets 16, 635–650.
Gotte G, Laurents DV, Merlino A, Picone D et al. (2013) Structural and functional relationships of natural and artificial dimeric bovine ribonucleases: new scaffolds for potential antitumor drugs. FEBS Lett 587, 3601-3608.
Gotte G, Menegazzi M (2019) Biological activities of secretory RNases: Focus on their oligomerization to design antitumor drugs. Front Immunol 10, 2626.
Graça VC, Silva MS, Reis LV, Sousa F et al. (2014) Ethylenediamine-Derived Chromatographic Ligand to Separate BSA, Lysozyme, and RNase A. Chromatographia 77, 1529–1537.
Guillem P, Jiarui L, Fatima A, Helena L et al. (2019) Testing a human antimicrobial RNase chimera against bacterial resistance. Frontiers in Microbiology 10, 1357.
Haigis MC, Kurten EL, Abel RL, Raines RT (2002) KFERQ sequence in ribonuclease A-mediated cytotoxicity. J Biol Chem 277, 11576 -11581.
Haigis MC, Raines RT (2003) Secretory ribonucleases are internalized by a dynamin-independent endocytic pathway. J Cell Sci 116, 313-24.
Jordaan S, Akinrinmade OA, Nachreiner T, Cremer C et al. (2018) Updates in the development of immunoRNases for the selective killing of tumor cells. Biomedicines 6, 28.
Kanwar SS, Kumar R (2017) Ribonuclease as Anticancer Therapeutics. Enz Eng 6, 162.
Kanwar SS, Mishra P, Meena KR (2016) Ribonucleases and their applications. J Adv Biotechnol Bioeng 4, 17-26.
Kobe B, Deisenhofer J (1996) Mechanism of ribonuclease inhibition by ribonuclease inhibitor protein based on the crystal structure of its complex with ribonuclease A. J Mol Biol 264, 1028-1043.
Lee SY, Kang MS, Jeong WY, Han DW et al. (2020) Hyaluronic acid-based theranostic nanomedicines for targeted cancer therapy. Cancers 12, 940.
Lee HH, Wang YN, Hung MC (2019) Functional roles of the human ribonuclease A superfamily in RNA metabolism and membrane receptor biology. Mol Aspects Med 70, 106–16.
Leich F, Koditz J, Ulbrich-Hofman R, Arnold U (2006) Tandemization endows bovine pancreatic ribonuclease with cytotoxic activity. J Mol Biol 358, 1305–1313.
Liu M, Gou F (2018) Recent updates on cancer immunotherapy. Precis Clin Med 1, 65–74.
Lomax JE, Bianchetti CM, Chang A, Phillips GN et al. (2014) Functional evolution of ribonuclease inhibitor: Insights from birds and reptiles. J Mol Biol 426, 3041–3056.
Makarov AA, Kolchinsky A, Ilinskaya ON (2008) Binase and other microbial RNases as potential anticancer agents. Bioessays 30, 781-90.
Mitkevich VA, Makarov AA, Ilinskaya ON (2014) Cell targets of antitumor ribonucleases. Mol Bio 48, 181-188.
Mohammadabadi MR, Mozafari MR (2019) Enhanced efficacy and bioavailability of thymoquinone using nanoliposomal dosage form. J Drug Delivery Sci Technol 47, 445–453.
Olmo N, Turnay J, Buitrago GG (2001) Cytotoxic mechanism of the ribotoxin-sarcin induction of cell death via apoptosis. Eur J Biochem 268, 2113-2123.
Olombrada M, Lazaro-Gorines R, Lopez-Rodriguez JC (2017) Fungal ribotoxins: A review of potential biotechnological applications. Toxins (Basel. 9, 71.
Pochechueva T, Alam S, Schötzau A, Chinarev A et al. (2017) Naturally occurring anti-glycan antibodies binding to Globo H-expressing cells identify ovarian cancer patients. J Ovarian Res 10, 8.
Pouckova P, Skvor J, Gotte G, Vottariello F et al. (2006) Some biological actions of PEG-conjugated RNase A oligomers. Neoplasma 53, 79–85.
Riccio G, D’Avino C, Raines RT, De Lorenzo C (2013) A novel fully human antitumor ImmunoRNase resistant to the RNase inhibitor. Protein Eng Des Sel 26, 243–248.
Roiz L, Smirnoff P, Bar-Eli M, Schwartz B et al. (2006) ACTIBIND, an actin-binding fungal T2-RNase with antiangiogenic and anticarcinogenic characteristics. Cancer 106, 2295–308.
Saxena A, Saxena SK, Shogen K (2009) Effect of Onconase on double-stranded RNA in vitro. Anticancer Res 29, 1067-71.
Schwartz B, Shoseyov O, Melnikova VO, McCarty M et al. (2007) Cancer Research 67, 5258-5266.
Suhasini AN, Sirdeshmukh R (2006) Transfer RNA cleavages by onconase reveal unusual cleavage sites. J Biol Chem 281, 12201-12209.
Suhasini AN, Sirdeshmukh R (2007) Onconase action on tRNA (Lys3), the primer for HIV-1 reverse transcription. Biophys Res Commun 363, 304-309.
Shruti G, Sukhdev S, Shamsher K (2016) An overview on ribonuclease and their therapeutic effects. Insight Med 1, 1-11.
Suri S, Panda B, Javed S, Mohd A (2007) RNase: A novel enzyme for treatment of cancers. Internet J Oncol 5, 1-5.
Wang X, Li Y, Li Q (2017) Hyaluronic acid modification of RNase and its intracellular delivery using lipid-like nanoparticles. J Control Release 263, 39-45.
Wang Z, Tang Y, Xie L, Huang A et al. (2019) The Prognostic and Clinical Value of CD44 in Colorectal Cancer: A Meta-Analysis. Front. Oncol. 9, 309.
Wu L, Xu Y, Zhao H, Li Y (2020) RNase T2 in inflammation and cancer: Immunological and biological views. Front. Immunol 11, 1554.
Yuki S, Kondo Y, Kato F (2004) Noncytotoxic ribonuclease, RNase T1, induces tumor cell death via hemagglutinating virus of Japan envelope vector. Eur J Biochem 271, 3567-72.
Zhang H, Chen J (2018) Current status and future directions of cancer immunotherapy. J Cancer 9, 1773–1781.