Generic placeholder image

Venoms and Toxins

Editor-in-Chief

ISSN (Print): 2666-1217
ISSN (Online): 2666-1225

Research Article

The Alcoholic Bark Extract of Terminalia Arjuna Exhibits Cytotoxic and Cytostatic Activity on Jurkat Leukemia Cells

Author(s): Giulia Greco, Eleonora Turrini, Massimo Tacchini, Immacolata Maresca and Carmela Fimognari*

Volume 1, Issue 1, 2021

Published on: 01 June, 2020

Page: [56 - 66] Pages: 11

DOI: 10.2174/2666121701999200601170928

Abstract

Background: Natural products are characterized by a complex chemical composition and are capable of concurrently modulate several signalling pathways. Considering the biological complexity of carcinogenesis, natural products represent key components of the therapeutic armamentarium for oncological diseases. The bark of Terminalia arjuna is used in traditional Ayurvedic medicine for its astringent, expectorant, cardiotonic, styptic, and antidysenteric properties. Alongside its traditional uses, Terminalia arjuna exhibits different biological activities including antimutagenic and anticarcinogenic.

Objective: This study was designed to evaluate the toxic effects of an alcoholic extract obtained from the bark of T. arjuna on a human T-lymphoblastic cell line (Jurkat). We explored the phytochemical composition and investigated the cytotoxic, cytostatic, genotoxic, and anti-genotoxic effects.

Methods: The phytochemical composition was analyzed using spectrophotometric methods; all the biological endpoints were assessed through flow cytometry.

Results: The phytochemical screening showed that polyphenols represent about 64% of the extract. Moreover, the extract was cytotoxic on Jurkat cells by inducing both apoptosis and necrosis, and blocked the cell cycle in the G2/M phase. Additionally, it was found that the extract lacks any genotoxic effect, but was not effective in protecting Jurkat cells from the DNA damage induced by H2O2 and etoposide.

Conclusion: The results of our study show the toxic effects of Terminalia arjuna on Jurkat cells and confirm the pivotal role played by natural compounds in the oncological field. Further studies should be performed to better understand its clinical potential and deepen its toxicological profile.

Keywords: Terminalia arjuna, leukemia cells, cytotoxicity, cell cycle, genotoxicity, antigenotoxicity.

Graphical Abstract
[1]
Available from: Cancer today [Internet] http://gco.iarc.fr/today/home [cited 2019 Sep 12].
[2]
Alqahtani A, Khan Z, Alloghbi AS. Said Ahmed T, Ashraf M, M. Hammouda D. Hepatocellular Carcinoma: Molecular Mechanisms and Targeted Therapies. Medicina (Mex) 2019; 55(9): 526.
[http://dx.doi.org/10.3390/medicina55090526]
[3]
Ramsay RR, Popovic-Nikolic MR, Nikolic K, Uliassi E, Bolognesi ML. A perspective on multi-target drug discovery and design for complex diseases. Clin Transl Med 2018; 7(1): 3.
[http://dx.doi.org/10.1186/s40169-017-0181-2] [PMID: 29340951]
[4]
Dar RA, Shahnawaz M, Rasool S, Qazi PH. Natural product medicines: A literature update. J Phytopharm 2017; 6(6): 340-2.
[5]
Howes MR. The evolution of anticancer drug discovery from plants. Lancet Oncol 2018; 19(3): 293-4.
[http://dx.doi.org/10.1016/S1470-2045(18)30136-0] [PMID: 29508748]
[6]
Nobili S, Lippi D, Witort E, et al. Natural compounds for cancer treatment and prevention. Pharmacol Res 2009; 59(6): 365-78.
[http://dx.doi.org/10.1016/j.phrs.2009.01.017] [PMID: 19429468]
[7]
Newman DJ, Cragg GM. Natural Products as Sources of New Drugs from 1981 to 2014. J Nat Prod 2016; 79(3): 629-61.
[http://dx.doi.org/10.1021/acs.jnatprod.5b01055] [PMID: 26852623]
[8]
Turrini E, Maffei F, Milelli A, Calcabrini C, Fimognari C. Overview of the Anticancer Profile of Avenanthramides from Oat. Int J Mol Sci 2019; 20(18): E4536.
[http://dx.doi.org/10.3390/ijms20184536] [PMID: 31540249]
[9]
Catanzaro E, Greco G, Potenza L, Calcabrini C, Fimognari C. Natural Products to Fight Cancer: A Focus on Juglans regia. Toxins (Basel) 2018; 10(11): E469.
[http://dx.doi.org/10.3390/toxins10110469] [PMID: 30441778]
[10]
Mondal A, Gandhi A, Fimognari C, Atanasov AG, Bishayee A. Alkaloids for cancer prevention and therapy: Current progress and future perspectives. Eur J Pharmacol 2019.: 858172472.
[http://dx.doi.org/10.1016/j.ejphar.2019.172472] [PMID: 31228447]
[11]
Turrini E, Catanzaro E, Ferruzzi L, et al. Hemidesmus indicus induces apoptosis via proteasome inhibition and generation of reactive oxygen species. Sci Rep 2019; 9(1): 7199.
[http://dx.doi.org/10.1038/s41598-019-43609-5] [PMID: 31076590]
[12]
Turrini E, Calcabrini C, Tacchini M, Efferth T, Sacchetti G, Guerrini A, et al. Vitro Study of the Cytotoxic, Cytostatic, and Antigenotoxic Profile of Hemidesmus indicus (L.) R.Br. (Apocynaceae) Crude Drug Extract on T Lymphoblastic Cells. Toxins 2018; 0610(02)
[13]
Turrini E, Catanzaro E, Muraro MG, et al. Hemidesmus indicus induces immunogenic death in human colorectal cancer cells. Oncotarget 2018; 9(36): 24443-56.
[http://dx.doi.org/10.18632/oncotarget.25325] [PMID: 29849952]
[14]
Turrini E, Ferruzzi L, Fimognari C. Natural compounds to overcome cancer chemoresistance: toxicological and clinical issues. Expert Opin Drug Metab Toxicol 2014; 10(12): 1677-90.
[http://dx.doi.org/10.1517/17425255.2014.972933] [PMID: 25339439]
[15]
Chopra RN, Ghosh S. Terminalia Arjuna: Its Chemistry, Pharmacology and Therapeutic Action. Ind Med Gaz 1929; 64(2): 70-3.
[PMID: 29009552]
[16]
Biswas M, Bhattacharya S, Ghosh AK, et al. Antitumour activity of Terminalia arjuna leaf against Ehrlich ascites carcinoma in mice. Nat Prod Res 2012; 26(12): 1141-4.
[http://dx.doi.org/10.1080/14786419.2011.561206] [PMID: 22017259]
[17]
Dwivedi S, Chopra D. Revisiting Terminalia arjuna - An Ancient Cardiovascular Drug. J Tradit Complement Med 2014; 4(4): 224-31.
[http://dx.doi.org/10.4103/2225-4110.139103] [PMID: 25379463]
[18]
Harborne JB. Indian Medicinal Plants. A Compendium of 500 Species.J Pharm Pharmacol Warrier P K, Nambiar V P K, Ramankutty C. 1994; Vol.1: pp. (11)935-5.
[19]
Jain S, Yadav PP, Gill V, Vasudeva N, Singla N. Terminalia arjuna a sacred medicinal plant: phytochemical and pharmacological profile. Phytochem Rev 2009; 8(2): 491-502.
[http://dx.doi.org/10.1007/s11101-009-9134-8]
[20]
Aneja KR, Sharma C, Joshi R. Antimicrobial activity of Terminalia arjuna Wight & Arn.: an ethnomedicinal plant against pathogens causing ear infection. Rev Bras Otorrinolaringol (Engl Ed) 2012; 78(1): 68-74.
[PMID: 22392241]
[21]
Mandal S, Patra A, Samanta A, et al. Analysis of phytochemical profile of Terminalia arjuna bark extract with antioxidative and antimicrobial properties. Asian Pac J Trop Biomed 2013; 3(12): 960-6.
[http://dx.doi.org/10.1016/S2221-1691(13)60186-0] [PMID: 24093787]
[22]
Cheng H-Y, Lin C-C, Lin T-C. Antiherpes simplex virus type 2 activity of casuarinin from the bark of Terminalia arjuna Linn. Antiviral Res 2002; 55(3): 447-55.
[http://dx.doi.org/10.1016/S0166-3542(02)00077-3] [PMID: 12206882]
[23]
Sharma SK, Sharma D, Agarwal N. Diminishing effect of arjuna tree (Terminalia arjuna) bark on the lipid and oxidative stress status of high fat high cholesterol fed rats and development of certain dietary recipes containing the tree bark for human consumption. Res Pharm 2012; 2: 22-30.
[24]
Subramaniam S, Ramachandran S, Uthrapathi S, Gnamanickam VR, Dubey GP. Anti-hyperlipidemic and antioxidant potential of different fractions of Terminalia arjuna Roxb. bark against PX- 407 induced hyperlipidemia. Indian J Exp Biol 2011; 49(4): 282-8.
[PMID: 21614892]
[25]
Gauthaman K, Mohamed Saleem TS, Ravi V. Sita Sharan Patel, Niranjali Devaraj S. Alcoholic Extract of Terminalia Arjuna Protects Rabbit Heart against Ischemic-Reperfusion Injury: Role of Antioxidant Enzymes and Heat Shock Protein. Int J Biol Life Agric Sci 2008; 2(6): 112-22.
[26]
Gauthaman K, Maulik M, Kumari R, Manchanda SC, Dinda AK, Maulik SK. Effect of chronic treatment with bark of Terminalia arjuna: a study on the isolated ischemic-reperfused rat heart. J Ethnopharmacol 2001; 75(2-3): 197-201.
[http://dx.doi.org/10.1016/S0378-8741(01)00183-0] [PMID: 11297851]
[27]
Parveen A, Babbar R, Agarwal S, Kotwani A, Fahim M. Mechanistic clues in the cardioprotective effect of Terminalia arjuna bark extract in isoproterenol-induced chronic heart failure in rats. Cardiovasc Toxicol 2011; 11(1): 48-57.
[http://dx.doi.org/10.1007/s12012-010-9099-2] [PMID: 21116736]
[28]
Sivalokanathan S, Ilayaraja M, Balasubramanian MP. Antioxidant activity of Terminalia arjuna bark extract on N-nitrosodiethylamine induced hepatocellular carcinoma in rats. Mol Cell Biochem 2006; 281(1-2): 87-93.
[http://dx.doi.org/10.1007/s11010-006-0433-8] [PMID: 16328960]
[29]
Sinha M, Manna P, Sil PC. Terminalia arjuna protects mouse hearts against sodium fluoride-induced oxidative stress. J Med Food 2008; 11(4): 733-40.
[http://dx.doi.org/10.1089/jmf.2007.0130] [PMID: 19053867]
[30]
Verma N, Vinayak M. Effect of Terminalia arjuna on antioxidant defense system in cancer. Mol Biol Rep 2009; 36(1): 159-64.
[http://dx.doi.org/10.1007/s11033-008-9279-3] [PMID: 18537039]
[31]
Reddy TK, Seshadri P, Reddy KKR, Jagetia GC, Reddy CD. Effect of Terminalia arjuna extract on adriamycin-induced DNA damage. Phytother Res 2008; 22(9): 1188-94.
[http://dx.doi.org/10.1002/ptr.2428] [PMID: 18729254]
[32]
Kaur S, Grover IS, Kumar S. Antimutagenic potential of extracts isolated from Terminalia arjuna. J Environ Pathol Toxicol Oncol 2001; 20(1): 9-14.
[http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.v20.i1.20] [PMID: 11215710]
[33]
Saxena M, Faridi U, Mishra R, et al. Cytotoxic agents from Terminalia arjuna. Planta Med 2007; 73(14): 1486-90.
[http://dx.doi.org/10.1055/s-2007-990258] [PMID: 18008199]
[34]
Ahmad MS, Ahmad S, Gautam B, Arshad M, Afzal M. Terminalia arjuna, a herbal remedy against environmental carcinogenicity: An in vitro and in vivo study. Egypt J Med Hum Genet 2014; 15(1): 61-7.
[http://dx.doi.org/10.1016/j.ejmhg.2013.10.004]
[35]
Viswanatha GL shastry, Vaidya SK, C R, Krishnadas N, Rangappa S. Antioxidant and antimutagenic activities of bark extract of Terminalia arjuna. Asian Pac J Trop Med 2010; 3(12): 965-70.
[http://dx.doi.org/10.1016/S1995-7645(11)60010-2]
[36]
Scassellati-Sforzolini G, Villarini LM, Moretti LM, et al. Antigenotoxic properties of Terminalia arjuna bark extracts. J Environ Pathol Toxicol Oncol 1999; 18(2): 119-25.
[PMID: 15281223]
[37]
Tacchini M, Spagnoletti A, Marieschi M, et al. Phytochemical profile and bioactivity of traditional ayurvedic decoctions and hydro-alcoholic macerations of Boerhaavia diffusa L. and Curculigo orchioides Gaertn. Nat Prod Res 2015; 29(22): 2071-9.
[http://dx.doi.org/10.1080/14786419.2014.1003299] [PMID: 25612143]
[38]
Lamaison JLC, Carnet A. Teneurs en Principaux Flavonoides des Fleurs de Crataegus monogyna Jacq et de Crataegus laevigata (Poiret D. C) en Fonction de la Vegetation. Pharm Acta Helv 1990; 65: 315-20.
[39]
Porter LJ, Hrstich LN, Chan BG. The conversion of procyanidins and prodelphinidins to cyanidin and delphinidin. Phytochemistry 1985; 25(1): 223-30.
[http://dx.doi.org/10.1016/S0031-9422(00)94533-3]
[40]
Bryce SM, Bemis JC, Avlasevich SL, Dertinger SD. In vitro micronucleus assay scored by flow cytometry provides a comprehensive evaluation of cytogenetic damage and cytotoxicity. Mutat Res 2007; 630(1-2): 78-91.
[http://dx.doi.org/10.1016/j.mrgentox.2007.03.002] [PMID: 17434794]
[41]
Gupta S, Bishnoi JP, Kumar N, Kumar H, Nidheersh T. Terminalia arjuna (Roxb.) Wight &Arn.: Competent source of bioactive components in functional food and drugs. J Pharm Innov 2018; 7(3): 223-31.
[42]
Lin Y, Shi R, Wang X, Shen H-M. Luteolin, a flavonoid with potential for cancer prevention and therapy. Curr Cancer Drug Targets 2008; 8(7): 634-46.
[http://dx.doi.org/10.2174/156800908786241050] [PMID: 18991571]
[43]
Toden S, Ravindranathan P, Gu J, Cardenas J, Yuchang M, Goel A. Oligomeric proanthocyanidins (OPCs) target cancer stem-like cells and suppress tumor organoid formation in colorectal cancer. Sci Rep 2018; 8(1): 3335.
[http://dx.doi.org/10.1038/s41598-018-21478-8] [PMID: 29463813]
[44]
Ravindranathan P, Pasham D, Balaji U, et al. Mechanistic insights into anticancer properties of oligomeric proanthocyanidins from grape seeds in colorectal cancer. Carcinogenesis 2018; 39(6): 767-77.
[http://dx.doi.org/10.1093/carcin/bgy034] [PMID: 29684110]
[45]
Rauf A, Imran M, Abu-Izneid T, et al. Proanthocyanidins: A comprehensive review. Biomed Pharmacother 2019.: 116108999.
[http://dx.doi.org/10.1016/j.biopha.2019.108999] [PMID: 31146109]
[46]
Saha A, Pawar VM, Jayaraman S. Characterisation of Polyphenols in Terminalia arjuna Bark Extract. Indian J Pharm Sci 2012; 74(4): 339-47.
[http://dx.doi.org/10.4103/0250-474X.107067] [PMID: 23626389]
[47]
Akhtar MJ, Alhadlaq HA, Kumar S, Alrokayan SA, Ahamed M. Selective cancer-killing ability of metal-based nanoparticles: implications for cancer therapy. Arch Toxicol 2015; 89(11): 1895-907.
[http://dx.doi.org/10.1007/s00204-015-1570-1] [PMID: 26223318]
[48]
Baudino TA. Targeted Cancer Therapy: The Next Generation of Cancer Treatment. Curr Drug Discov Technol 2015; 12(1): 3-20.
[http://dx.doi.org/10.2174/1570163812666150602144310] [PMID: 26033233]
[49]
Lee S-H, Meng XW, Flatten KS, Loegering DA, Kaufmann SH. Phosphatidylserine exposure during apoptosis reflects bidirectional trafficking between plasma membrane and cytoplasm. Cell Death Differ 2013; 20(1): 64-76.
[http://dx.doi.org/10.1038/cdd.2012.93] [PMID: 22858544]
[50]
Zimmermann M, Meyer N. Annexin V/7-AAD staining in keratinocytes. Methods Mol Biol 2011; 740: 57-63.
[http://dx.doi.org/10.1007/978-1-61779-108-6_8] [PMID: 21468968]
[51]
Green DR, Llambi F. Cell Death Signaling. Cold Spring Harb Perspect Biol 2015; 7(12): a006080.
[http://dx.doi.org/10.1101/cshperspect.a006080] [PMID: 26626938]
[52]
Galluzzi L, Vitale I, Aaronson SA, et al. Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018. Cell Death Differ 2018; 25(3): 486-541.
[http://dx.doi.org/10.1038/s41418-017-0012-4] [PMID: 29362479]
[53]
D’Arcy MS. Cell death: a review of the major forms of apoptosis, necrosis and autophagy. Cell Biol Int 2019; 43(6): 582-92.
[http://dx.doi.org/10.1002/cbin.11137] [PMID: 30958602]
[54]
Tait SWG, Ichim G, Green DR. Die another way--non-apoptotic mechanisms of cell death. J Cell Sci 2014; 127(Pt 10): 2135-44.
[http://dx.doi.org/10.1242/jcs.093575] [PMID: 24833670]
[55]
Giorgi C, Romagnoli A, Pinton P, Rizzuto R. Ca2+ signaling, mitochondria and cell death. Curr Mol Med 2008; 8(2): 119-30.
[http://dx.doi.org/10.2174/156652408783769571] [PMID: 18336292]
[56]
Salomon AR, Voehringer DW, Herzenberg LA, Khosla C. Understanding and exploiting the mechanistic basis for selectivity of polyketide inhibitors of F(0)F(1)-ATPase. Proc Natl Acad Sci USA 2000; 97(26): 14766-71.
[http://dx.doi.org/10.1073/pnas.97.26.14766] [PMID: 11121076]
[57]
Li Y-Z, Li CJ, Pinto AV, Pardee AB. Release of mitochondrial cytochrome C in both apoptosis and necrosis induced by β-lapachone in human carcinoma cells. Mol Med 1999; 5(4): 232-9.
[http://dx.doi.org/10.1007/BF03402120] [PMID: 10448645]
[58]
Tagliarino C, Pink JJ, Dubyak GR, Nieminen AL, Boothman DA. Calcium is a key signaling molecule in beta-lapachone-mediated cell death. J Biol Chem 2001; 276(22): 19150-9.
[http://dx.doi.org/10.1074/jbc.M100730200] [PMID: 11279125]
[59]
Bai X, Cerimele F, Ushio-Fukai M, et al. Honokiol, a small molecular weight natural product, inhibits angiogenesis in vitro and tumor growth in vivo. J Biol Chem 2003; 278(37): 35501-7.
[http://dx.doi.org/10.1074/jbc.M302967200] [PMID: 12816951]
[60]
Nagpal A, Meena LS, Kaur S, Grover IS, Wadhwa R, Kaul SC. Growth suppression of human transformed cells by treatment with bark extracts from a medicinal plant, Terminalia arjuna. In Vitro Cell Dev Biol Anim 2000; 36(8): 544-7.
[http://dx.doi.org/10.1290/1071-2690(2000)036<0544:GSOHTC>2.0.CO;2] [PMID: 11149755]
[61]
Shalini S, Kumar RR, Birendra S. Antiproliferative effect of Phytosome complex of Methanolic extact of Terminalia Arjuna bark on Human Breast Cancer Cell Lines (MCF-7). Int J Drug Dev & Res 2015; 7(1): 173-82.
[62]
Singh S, Verma SK, Singh SK. Analysis of anti-cancer potential of Terminalia arjuna. Int J Adv Scient Res Manage 2017; 2(11): 82-7.
[63]
Sivalokanathan S, Vijayababu MR, Balasubramanian MP. Effects of Terminalia arjuna bark extract on apoptosis of human hepatoma cell line HepG2. World J Gastroenterol 2006; 12(7): 1018-24.
[http://dx.doi.org/10.3748/wjg.v12.i7.1018] [PMID: 16534840]
[64]
Kuo P-L, Hsu Y-L, Lin T-C, Chang J-K, Lin C-C. Induction of cell cycle arrest and apoptosis in human non-small cell lung cancer A549 cells by casuarinin from the bark of Terminalia arjuna Linn. Anticancer Drugs 2005; 16(4): 409-15.
[http://dx.doi.org/10.1097/00001813-200504000-00007] [PMID: 15746577]
[65]
Kuo P-L, Hsu Y-L, Lin T-C, Lin L-T, Chang J-K, Lin C-C. Casuarinin from the bark of Terminalia arjuna induces apoptosis and cell cycle arrest in human breast adenocarcinoma MCF-7 cells. Planta Med 2005; 71(3): 237-43.
[http://dx.doi.org/10.1055/s-2005-837823] [PMID: 15770544]
[66]
Zhang L-J, Cheng J-J, Liao C-C, et al. Triterpene acids from Euscaphis japonica and assessment of their cytotoxic and anti-NO activities. Planta Med 2012; 78(14): 1584-90.
[http://dx.doi.org/10.1055/s-0032-1315040] [PMID: 22814889]
[67]
Joo H, Lee HJ, Shin EA, et al. c-Jun N-terminal Kinase-Dependent Endoplasmic Reticulum Stress Pathway is Critically Involved in Arjunic Acid Induced Apoptosis in Non-Small Cell Lung Cancer Cells. Phytother Res 2016; 30(4): 596-603.
[http://dx.doi.org/10.1002/ptr.5563] [PMID: 26787261]
[68]
Elsherbiny NM, Al-Gayyar MMH. Anti-tumor activity of arjunolic acid against Ehrlich Ascites Carcinoma cells in vivo and in vitro through blocking TGF-β type 1 receptor. Biomed Pharmacother 2016; 82: 28-34.
[http://dx.doi.org/10.1016/j.biopha.2016.04.046] [PMID: 27470335]
[69]
Keith CT, Borisy AA, Stockwell BR. Multicomponent therapeutics for networked systems. Nat Rev Drug Discov 2005; 4(1): 71-8.
[http://dx.doi.org/10.1038/nrd1609] [PMID: 15688074]
[70]
Mills CC, Kolb EA, Sampson VB. Development of Chemotherapy with Cell-Cycle Inhibitors for Adult and Pediatric Cancer Therapy. Cancer Res 2018; 78(2): 320-5.
[http://dx.doi.org/10.1158/0008-5472.CAN-17-2782] [PMID: 29311160]
[71]
Malumbres M, Barbacid M. Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer 2009; 9(3): 153-66.
[http://dx.doi.org/10.1038/nrc2602] [PMID: 19238148]
[72]
Bae SY, Kim GD, Jeon J-E, Shin J, Lee SK. Anti-proliferative effect of (19Z)-halichondramide, a novel marine macrolide isolated from the sponge Chondrosia corticata, is associated with G2/M cell cycle arrest and suppression of mTOR signaling in human lung cancer cells. Toxicol In Vitro 2013; 27(2): 694-9.
[http://dx.doi.org/10.1016/j.tiv.2012.11.001] [PMID: 23147639]
[73]
Malumbres M, Barbacid M. To cycle or not to cycle: a critical decision in cancer. Nat Rev Cancer 2001; 1(3): 222-31.
[http://dx.doi.org/10.1038/35106065] [PMID: 11902577]
[74]
Massagué J. G1 cell-cycle control and cancer. Nature 2004; 432(7015): 298-306.
[http://dx.doi.org/10.1038/nature03094] [PMID: 15549091]
[75]
Henriques AC, Ribeiro D, Pedrosa J, Sarmento B, Silva PMA, Bousbaa H. Mitosis inhibitors in anticancer therapy: When blocking the exit becomes a solution. Cancer Lett 2019; 440-441: 64-81.
[http://dx.doi.org/10.1016/j.canlet.2018.10.005] [PMID: 30312726]
[76]
Araldi RP, de Melo TC, Mendes TB, et al. Using the comet and micronucleus assays for genotoxicity studies: A review. Biomed Pharmacother 2015; 72: 74-82.
[http://dx.doi.org/10.1016/j.biopha.2015.04.004] [PMID: 26054678]
[77]
Urquiaga I, Leighton F. Plant polyphenol antioxidants and oxidative stress. Biol Res 2000; 33(2): 55-64.
[http://dx.doi.org/10.4067/S0716-97602000000200004] [PMID: 15693271]
[78]
Niedzwiecki A, Roomi MW, Kalinovsky T, Rath M. Anticancer Efficacy of Polyphenols and Their Combinations. Nutrients 2016; 8(9): E552.
[http://dx.doi.org/10.3390/nu8090552] [PMID: 27618095]
[79]
Abbaszadeh H, Keikhaei B, Mottaghi S. A review of molecular mechanisms involved in anticancer and antiangiogenic effects of natural polyphenolic compounds. Phytother Res 2019; 33(8): 2002-14.
[http://dx.doi.org/10.1002/ptr.6403] [PMID: 31373113]
[80]
Kampa M, Nifli A-P, Notas G, Castanas E. Polyphenols and cancer cell growth. Rev Physiol Biochem Pharmacol 2007; 159: 79-113.
[PMID: 17551696]
[81]
Guthrie AR, Chow HS, Martinez JA. Effects of resveratrol on drug- and carcinogen-metabolizing enzymes, implications for cancer prevention. Pharmacol Res Perspect 2017; 5(1): e00294.
[http://dx.doi.org/10.1002/prp2.294] [PMID: 28596842]
[82]
Kuntz S, Wenzel U, Daniel H. Comparative analysis of the effects of flavonoids on proliferation, cytotoxicity, and apoptosis in human colon cancer cell lines. Eur J Nutr 1999; 38(3): 133-42.
[http://dx.doi.org/10.1007/s003940050054] [PMID: 10443335]
[83]
Curti V, Di Lorenzo A, Dacrema M, Xiao J, Nabavi SM, Daglia M. In vitro polyphenol effects on apoptosis: An update of literature data. Semin Cancer Biol 2017; 46: 119-31.
[http://dx.doi.org/10.1016/j.semcancer.2017.08.005] [PMID: 28830771]
[84]
Khan F, Niaz K, Maqbool F, et al. Molecular Targets Underlying the Anticancer Effects of Quercetin: An Update. Nutrients 2016; 8(9): E529.
[http://dx.doi.org/10.3390/nu8090529] [PMID: 27589790]
[85]
Coccia A, Mosca L, Puca R, Mangino G, Rossi A, Lendaro E. Extra-virgin olive oil phenols block cell cycle progression and modulate chemotherapeutic toxicity in bladder cancer cells. Oncol Rep 2016; 36(6): 3095-104.
[http://dx.doi.org/10.3892/or.2016.5150] [PMID: 27748855]
[86]
Zielińska-Przyjemska M, Kaczmarek M, Krajka-Kuźniak V, Łuczak M, Baer-Dubowska W. The effect of resveratrol, its naturally occurring derivatives and tannic acid on the induction of cell cycle arrest and apoptosis in rat C6 and human T98G glioma cell lines. Toxicol In Vitro 2017; 43: 69-75.
[http://dx.doi.org/10.1016/j.tiv.2017.06.004] [PMID: 28595835]
[87]
Oak M-H, El Bedoui J, Schini-Kerth VB. Antiangiogenic properties of natural polyphenols from red wine and green tea. J Nutr Biochem 2005; 16(1): 1-8.
[http://dx.doi.org/10.1016/j.jnutbio.2004.09.004] [PMID: 15629234]
[88]
Sarkar J, Nandy SK, Chowdhury A, Chakraborti T, Chakraborti S. Inhibition of MMP-9 by green tea catechins and prediction of their interaction by molecular docking analysis. Biomed Pharmacother 2016; 84: 340-7.
[http://dx.doi.org/10.1016/j.biopha.2016.09.049] [PMID: 27668533]
[89]
Cerezo AB, Winterbone MS, Moyle CWA, Needs PW, Kroon PA. Molecular structure-function relationship of dietary polyphenols for inhibiting VEGF-induced VEGFR-2 activity. Mol Nutr Food Res 2015; 59(11): 2119-31.
[http://dx.doi.org/10.1002/mnfr.201500407] [PMID: 26250940]
[90]
Shanmugam MK, Warrier S, Kumar AP, Sethi G, Arfuso F. Potential Role of Natural Compounds as Anti-Angiogenic Agents in Cancer. Curr Vasc Pharmacol 2017; 15(6): 503-19.
[http://dx.doi.org/10.2174/1570161115666170713094319] [PMID: 28707601]
[91]
Majidinia M, Bishayee A, Yousefi B. Polyphenols: Major regulators of key components of DNA damage response in cancer. DNA Repair (Amst) 2019.: 82102679.
[http://dx.doi.org/10.1016/j.dnarep.2019.102679] [PMID: 31450085]
[92]
Azqueta A, Collins A. Polyphenols and DNA Damage: A Mixed Blessing. Nutrients 2016; 8(12): E785.
[http://dx.doi.org/10.3390/nu8120785] [PMID: 27918471]
[93]
Kelly MR, Xu J, Alexander KE, Loo G. Disparate effects of similar phenolic phytochemicals as inhibitors of oxidative damage to cellular DNA. Mutat Res 2001; 485(4): 309-18.
[http://dx.doi.org/10.1016/S0921-8777(01)00066-0] [PMID: 11585363]
[94]
Ferguson LR. Role of plant polyphenols in genomic stability. Mutat Res 2001; 475(1-2): 89-111.
[http://dx.doi.org/10.1016/S0027-5107(01)00073-2] [PMID: 11295156]
[95]
Benhusein GM, Mutch E, Aburawi S, Williams FM. Genotoxic effect induced by hydrogen peroxide in human hepatoma cells using comet assay. Libyan J Med 2010; 5: 5.
[http://dx.doi.org/10.3402/ljm.v5i0.4637] [PMID: 21483593]
[96]
Zanichelli F, Capasso S, Di Bernardo G, et al. Low concentrations of isothiocyanates protect mesenchymal stem cells from oxidative injuries, while high concentrations exacerbate DNA damage. Apoptosis 2012; 17(9): 964-74.
[http://dx.doi.org/10.1007/s10495-012-0740-3] [PMID: 22684843]
[97]
Meresse P, Dechaux E, Monneret C, Bertounesque E. Etoposide: discovery and medicinal chemistry. Curr Med Chem 2004; 11(18): 2443-66.
[http://dx.doi.org/10.2174/0929867043364531] [PMID: 15379707]
[98]
Kaur SJ, Grover IS, Kumar S. Modulatory effects of a tannin fraction isolated from Terminalia arjuna on the genotoxicity of mutagens in Salmonella typhimurium. Food Chem Toxicol 2000; 38(12): 1113-9.
[http://dx.doi.org/10.1016/S0278-6915(00)00104-6] [PMID: 11033200]
[99]
Pasquini R, Scassellati-Sforzolini G, Villarini M, et al. In vitro protective effects of Terminalia arjuna bark extracts against the 4-nitroquinoline-N-oxide genotoxicity. J Environ Pathol Toxicol Oncol 2002; 21(1): 33-44.
[http://dx.doi.org/10.1615/JEnvironPatholToxicolOncol.v21.i1.20] [PMID: 11934011]
[100]
Nohmi T. Thresholds of Genotoxic and Non-Genotoxic Carcinogens. Toxicol Res 2018; 34(4): 281-90.
[http://dx.doi.org/10.5487/TR.2018.34.4.281] [PMID: 30370002]
[101]
Shukla PC, Singh KK, Yanagawa B, Teoh H, Verma S. DNA damage repair and cardiovascular diseases. Can J Cardiol 2010; 26(Suppl. A): 13A-6A.
[http://dx.doi.org/10.1016/S0828-282X(10)71055-2]
[102]
Khan AO. Genetics of primary glaucoma. Curr Opin Ophthalmol 2011; 22(5): 347-55.
[http://dx.doi.org/10.1097/ICU.0b013e32834922d2] [PMID: 21730848]
[103]
Storkebaum E, Quaegebeur A, Vikkula M, Carmeliet P. Cerebrovascular disorders: molecular insights and therapeutic opportunities. Nat Neurosci 2011; 14(11): 1390-7.
[http://dx.doi.org/10.1038/nn.2947] [PMID: 22030550]

© 2022 Bentham Science Publishers | Privacy Policy