مطالعه تاثیر ضدآنتی‌اکسیدانی عصاره برگ رزماری و میوه توت‌فرنگی بر روی سلول‌های سرطانی معده
محورهای موضوعی : زیست شناسی
مهداد انکاری
1
(دکتری، گروه شیمی، دانشکده علوم پایه، موسسه آموزش عالی مهرآیین، بندرانزلی، ایران)
سمیرا گودرزی
2
(دکتری، گروه زیست‌شناسی، دانشکده علوم پایه، واحد ایذه، دانشگاه آزاد اسلامی، ایذه، ایران)
کیانا انصاری
3
(کارشناسی، گروه زیست‌شناسی، دانشکده علوم پایه، واحد تالش، دانشگاه پیام نور، تالش، ایران)
کلید واژه: ضدآنتی‌اکسیدان, عصاره برگ رزماری, سلول‌های سرطانی, سرطان معده, میوه توت‌فرنگی,
چکیده مقاله :
هدف: سرطان معده یکی از شایع‌ترین سرطان‌ها در جهان است که سبب مرگ و میرهای زیای در میان انسان‌ها می‌شود. هدف از انجام این پژوهش بررسی تاثیر ضد آنتی‌اکسیدانی عصاره برگ رزماری و میوه توت‌فرنگی بر روی سلول‌های سرطانی معده است. مواد و روش‌ها: پس از تهیه دو ماده گیاهی و عصاره‌گیری از آنها، اقدام به اندازه‌گیری توان آنتی اکسیدانی احیاء آهن(FRAP)، تاثیر سمّیت دو عصاره گیاهی مورد استفاده بر رشد و تکثیر سلول‌های سرطانی و فیبروبلاستی در غلظت‌های 5/0، 1، 5/1 و 2 میلی‌گرم بر میلی‌لیتر با روش MMT و بررسی میزان IC50 در دو عصاره گیاهی مورد سنجش برای زمان‌های 24، 48، 72 و 96 ساعت شد. از آزمون تحلیل واریانس یک راهه با سطح معناداری 05/0 برای آنالیز نتایج به دست آمده استفاده گردید. نتایج: نتایج نشان داد که بالاترین میزان FRAP برای عصاره میوه توت‌فرنگی و برگ رزماری در حلال آب به ترتیب با مقادیر 08/0±68/1 و 15/0±94/0 است. نتایج به دست آمده نشان داد که مقدار 2 میلی‌گرم بر میلی‌لیتر برای عصاره برگ رزماری و میوه توت‌فرنگی بهترین اثر را برای جلوگیری از رشد و تکثیر سلول‌های سرطانی و فیبروبلاستی دارد. مقادیر حاصل برای IC50 نشان داد که مقدار غلظت مورد نیاز برای مهار 50 درصد فعالیت آنتی اکسیدانی برای دو عصاره در زمان 96 ساعت دارای کم‌ترین مقدار است. نتیجه‌گیری: هر دو عصاره دارای اثرات ضد سرطانی بر روی رده سلولی AGS در سرطان معده هستند که میوه توت‌فرنگی داری اثر مناسب‌تری نسبت به برگ رزماری است.
Purpose and Problem: Stomach cancer is one of the most common cancers in the world that causes many deaths among humans. The aim of this study was to investigate the antioxidant effect of rosemary leaf extract (Rosmarinus officinalis) and strawberry (Fragaria vesca) on stomach cancer cells. Method: After preparing two plant substances and extracting them, measure the antioxidant power of iron regeneration (FRAP), the toxicity of the two plant extracts used on the growth and proliferation of cancer cells and fibroblasts in concentrations. 0.5, 1, 1.5 and 2 mg/ml were measured by MMT method and IC50 was measured in two plant extracts for 24, 48, 72 and 96 hours. One-way analysis of variance with a significance level of 0.05 was used to analyze the results. Results: The results showed that the highest FRAP levels for strawberry fruit and rosemary leaf extracts in water solvent were 1.68 ± 0.08 and 0.94± 0.15, respectively. The results showed that 2mg /ml for rosemary leaf extract and strawberry fruit has the best effect to prevent the growth and proliferation of cancer cells and fibroblasts. The values obtained for IC50 showed that the concentration required to inhibit 50% of the antioxidant activity for the two extracts at 96 h was the lowest. Conclusion: The results showed that both extracts have anti-cancer effects on AGS cell line in Stomach cancer that strawberry fruit has a more suitable effect than rosemary leaf.
Sotoudeh M, Mirsamadi MM & Sedghi M. Comparison of the type of intera cellular mucin in patients with pylori gastritis and normal population. Tehran Uni Med J. 2002; 29(1): 245-250.
Siegel R, Ma J, Zou Z & Jemal A. Cancer statistics. J. Clin. 2014; 64(1): 9-29.
Oliveira FJ, Ferrão H, Furtado E, Batista H & Conceição L. Early gastric cancer: report of 58cases. Gastric Cancer. 1998; 1(1): 51-6.
Fitsiou E, Mitropoulou G, Spyridopoulou K & Tiptiri-Kourpeti A. Phytochemical profile and evaluation of the biological activities of essential oils derived from the greek aromatic plant species Ocimum basilicum, Mentha spicata, Pimpinella anisum and Fortunella margarita. Molecules. 2016; 21(8): 1-15.
Yeh Lee Y & Derakhshan MH. Environmental and lifestyle risk factors of gastric cancer. Archives of Iranian Medicine. 2013; 16(6): 358-365.
Motavalizadeh Ardekani A, Hashemi M, Safakish M & Alem-Bagheri A. Medical Treatment of Cancer in Traditional Iranian Medicine. Journal of Islamic and Iranian Traditional Medicine. 2012; 3(1): 3-20.
Rafieian-Kopaei M. Medicinal plants and the human needs. HerbMed Pharmacology. 2012; 1(1): 1-2.
Greenwell G & Rahman P. Medicinal plants: their use in anticancer treatment.
Int J Pharm Sci Res. 2015; 6(10): 4103- 4112.
Kehkashan Arshad Q, Ahsana D, Bina SS, Nurul K & Huma A. Anticancer activity of Ocimum basilicum and the effect of ursolic acid on the cytoskeleton of MCF-7 human breast cancer cells. Letters in Drug Design & Discovery. 2010; 1(10): 726 -736.
Zargari A. Medicinal plant. 4thed. Tehran: Tehran Univercity Prss. 1969: 71-76
Dermarderosian A. The Review of NaturalProducts. 1st ed. Missouri: Wolters Kluwer Co. 2001; 2(12): 512-13.
Martinez-Lirola MJ, Gonzalez-Tejero MR & Molero-Mesa J. Ethanobotanical resources in the province of Almeria, Spain: Campos De Nijar. Econ Bot. 2016; 50(1): 40-56.
Ozcan M. Antioxidant activities of rosemary, sage, and sumac extracts and their combinations on stability of natural peanut oil. J. Med Food. 2003; 6(2): 267-70.
Kosaka K & Yokoi T. Carnosic acid, a component of rosemary (Rosmarinus officinalis L.), promotes synthesis of nerve growth factor in T98G human glioblastoma cells. Biol. Pharm. Bull. 2003; 26(1): 1620-30.
Moore J, Yousef M & Tsiani E. Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols. Nutrients. 2016; 8(1): 731-740.
Moore J, Megaly M, MacNeil AJ, Klentrou P & Tsiani E. Rosemary extract reduces Akt/mTOR/p70S6K activation and inhibits proliferation and survival of A549 human lung cancer cells. Biomed. Pharmacother. 2016; 83(2): 725-732.
Proestos Ch, Boziaris IS, Kapsokefalou M & Komaitis M. Natural Antioxidant Constituents from Selected Aromatic Plants and their Antimicrobial Activity Againts Selected Pathogenic Microorganism. Original Scientific Paper. 2008; 46(2): 151-156.
Yonghua Z, Shiow YW, Chien YW & Wei Z. Changes in Strawberry Phenolics, Antocyanins, and Antioxidant Capacity in Response to High Oxygen. Science Direct. 2017; 40(5): 49-57.
Sghaier MB & et al. Chemical Investigation of Different Crude Extracts from Teucrium Ramosissimum Leaves, Correlation with their Antigenotoxic and Antoxidant Properties. Food and Chemical Toxicology. 2019; 49(2): 191-201.
Dorosti N, Zarabi S, Ahmadi S & Rostami R. Anticancer activity evaluation of methanolic extract of Allium Jesdianum and Nectaroscordeum Coelzi against HeLa and K562 cell lines. Yafteh. 2017; 19(1): 31-41.
Yesil-Celiktas O, Sevimli C, Bedir E & Vardar-Sukan F. Inhibitory Effects of Rosemary Extracts, Carnosic Acid and Rosmarinic Acid on the Growth of Various Human Cancer Cell Lines. Plant Foods Human Nutrition. 2010; 65(6): 158-163.
Yasutaka Ikeda A & Hajime Ohigashi M. Ursolic acid: An anti- and pro-inflammatory triterpenoid. Mol. Nutr. Food Res. 2008; 52(1): 26-42.
Currier N, Solomon SE, Demicco EG & Chang D. Oncogenic Signaling Pathways Activated in DMBA-Induced Mouse Mammary Tumors. Toxicologic Pathology. 2005; 33(6): 726-737.
Majd A, Mehrabian S, Jonoobi P & Modaresi A. A Comparative Study of anti-mutation and anti-carcinogenic properties of Rosemary (Rosmarinus officinalis L.) and Lavender (Lavandula angustifolia Mill.) during their different developmental stages. Iran J Med Microbiol. 2011; 5(3): 61-67.
Lo AH, Liang YC, Lin-Shiau SY & Ho CT. Carnosol, an antioxidant in rosemary, suppresses inducible nitric oxide synthase through down-regulating nuclear factor-kappaB in mouse macrophages. Carcinogenesis. 2002; 23(6): 983-991.
Aggarwal BB, Ichikawa H, Garodia P & Weerasinghe P. From traditional Ayurvedic medicine to modern medicine: identification of therapeutic targets for suppression of inflammation and cancer. Oncologic, Endocrine & Metabolic. 2006; 10(1): 87-118.
Liang YC, Tsai SH, Tsai DC & Lin-Shiau SY. Suppression of inducible cyclooxygenase and nitric oxide synthase through activation of peroxisome proliferator-activated receptor-gamma by flavonoids in mouse macrophages. FEBS Letters. 2001;496(1): 12-8.
Serafini M, Bellocco R, Wolk A & Ekstrom AM. Total antioxidant potential of fruit and vegetables and risk of gastric cancer. Gastroenterology. 2002; 123(4): 985-91.
Cheng A, Lee M, Tsai ML & Lai CS. Rosmanol potently induces apoptosis through both the mitochondrial apoptotic pathway and death receptor pathway in human colon adenocarcinoma COLO 205 cells. Food and Chemical Toxicology. 2010; 12(3): 12-22.
Dorrie J, Sapala K & Zunino SJ. Carnosol-induced apoptosis and downregulation of Bcl-2 in B-lineage leukemia cells. Cancer Letters. 2001; 170(5): 33-39.
Huang MT, Ho CT, Wang ZY & Ho CT. Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and ursolic acid. Cancer Researches. 1994; 54(3): 701-708.
Fumagalli M & et al. Strawberry tannins inhibit IL-8 secretion in a cell model of gastric inflammation. Pharmacol. Res. 2016; 111(6): 703-712.
Alarcón M, Fuentes E, Olate N, Navarrete S, Carrasco G & Palomo I. Strawberry extract presents antiplatelet activity by inhibition of inflammatory mediator of atherosclerosis (sP-selectin, sCD40L, RANTES, and IL-1β) and thrombus formation. Platelets. 2015; 26(12): 224-229.
Roomiani L, Soltani M, Akhondzadeh Basti A, Mahmoodi A, Taheri Mirghaed A & Yadollahi F. Evaluation of the chemical composition and in vitro antimicrobial activity of Rosmarinus officinalis, Zataria multiflora, Anethum graveolens and Eucalyptus globulus against Streptococcus iniae the cause of zoonotic disease in farmed fish. IJFS. 2013; 12(3): 702-16.
Alvarez-Suarez JM, Dekanski D, Ristic´ S, Radonjic´ NV & Petronijevic´ ND. Strawberry Polyphenols Attenuate Ethanol-Induced Gastric Lesions in Rats by Activation of Antioxidant Enzymes and Attenuation of MDA Increase. PLoS ONE. 2019; 6(10):
258-278.
Tong C & et al. Randomized Phase II Trial of Lyophilized Strawberries in Patients With Dysplastic Precancerous Lesions of the Esophagus. Cancer Prev Res (Phila). 2018; 5(1): 41-50.
Wang B, Han Q & Zhu Y. Oxymatrine inhibited cell proliferation by inducing apoptosis in human lung cancer A549 cells. Bio-Med Mater Eng. 2015; 26(2): 165-172.
Dikshit P, Goswami A, Mishra A, Catterjee M & Jana NR. Curcumin induces stress response, neurite outgrowth and prevent NF-κB activation by inhibiting the proteasome function. Neurotox Res. 2006; 9(1): 29-37.
_||_Sotoudeh M, Mirsamadi MM & Sedghi M. Comparison of the type of intera cellular mucin in patients with pylori gastritis and normal population. Tehran Uni Med J. 2002; 29(1): 245-250.
Siegel R, Ma J, Zou Z & Jemal A. Cancer statistics. J. Clin. 2014; 64(1): 9-29.
Oliveira FJ, Ferrão H, Furtado E, Batista H & Conceição L. Early gastric cancer: report of 58cases. Gastric Cancer. 1998; 1(1): 51-6.
Fitsiou E, Mitropoulou G, Spyridopoulou K & Tiptiri-Kourpeti A. Phytochemical profile and evaluation of the biological activities of essential oils derived from the greek aromatic plant species Ocimum basilicum, Mentha spicata, Pimpinella anisum and Fortunella margarita. Molecules. 2016; 21(8): 1-15.
Yeh Lee Y & Derakhshan MH. Environmental and lifestyle risk factors of gastric cancer. Archives of Iranian Medicine. 2013; 16(6): 358-365.
Motavalizadeh Ardekani A, Hashemi M, Safakish M & Alem-Bagheri A. Medical Treatment of Cancer in Traditional Iranian Medicine. Journal of Islamic and Iranian Traditional Medicine. 2012; 3(1): 3-20.
Rafieian-Kopaei M. Medicinal plants and the human needs. HerbMed Pharmacology. 2012; 1(1): 1-2.
Greenwell G & Rahman P. Medicinal plants: their use in anticancer treatment.
Int J Pharm Sci Res. 2015; 6(10): 4103- 4112.
Kehkashan Arshad Q, Ahsana D, Bina SS, Nurul K & Huma A. Anticancer activity of Ocimum basilicum and the effect of ursolic acid on the cytoskeleton of MCF-7 human breast cancer cells. Letters in Drug Design & Discovery. 2010; 1(10): 726 -736.
Zargari A. Medicinal plant. 4thed. Tehran: Tehran Univercity Prss. 1969: 71-76
Dermarderosian A. The Review of NaturalProducts. 1st ed. Missouri: Wolters Kluwer Co. 2001; 2(12): 512-13.
Martinez-Lirola MJ, Gonzalez-Tejero MR & Molero-Mesa J. Ethanobotanical resources in the province of Almeria, Spain: Campos De Nijar. Econ Bot. 2016; 50(1): 40-56.
Ozcan M. Antioxidant activities of rosemary, sage, and sumac extracts and their combinations on stability of natural peanut oil. J. Med Food. 2003; 6(2): 267-70.
Kosaka K & Yokoi T. Carnosic acid, a component of rosemary (Rosmarinus officinalis L.), promotes synthesis of nerve growth factor in T98G human glioblastoma cells. Biol. Pharm. Bull. 2003; 26(1): 1620-30.
Moore J, Yousef M & Tsiani E. Anticancer Effects of Rosemary (Rosmarinus officinalis L.) Extract and Rosemary Extract Polyphenols. Nutrients. 2016; 8(1): 731-740.
Moore J, Megaly M, MacNeil AJ, Klentrou P & Tsiani E. Rosemary extract reduces Akt/mTOR/p70S6K activation and inhibits proliferation and survival of A549 human lung cancer cells. Biomed. Pharmacother. 2016; 83(2): 725-732.
Proestos Ch, Boziaris IS, Kapsokefalou M & Komaitis M. Natural Antioxidant Constituents from Selected Aromatic Plants and their Antimicrobial Activity Againts Selected Pathogenic Microorganism. Original Scientific Paper. 2008; 46(2): 151-156.
Yonghua Z, Shiow YW, Chien YW & Wei Z. Changes in Strawberry Phenolics, Antocyanins, and Antioxidant Capacity in Response to High Oxygen. Science Direct. 2017; 40(5): 49-57.
Sghaier MB & et al. Chemical Investigation of Different Crude Extracts from Teucrium Ramosissimum Leaves, Correlation with their Antigenotoxic and Antoxidant Properties. Food and Chemical Toxicology. 2019; 49(2): 191-201.
Dorosti N, Zarabi S, Ahmadi S & Rostami R. Anticancer activity evaluation of methanolic extract of Allium Jesdianum and Nectaroscordeum Coelzi against HeLa and K562 cell lines. Yafteh. 2017; 19(1): 31-41.
Yesil-Celiktas O, Sevimli C, Bedir E & Vardar-Sukan F. Inhibitory Effects of Rosemary Extracts, Carnosic Acid and Rosmarinic Acid on the Growth of Various Human Cancer Cell Lines. Plant Foods Human Nutrition. 2010; 65(6): 158-163.
Yasutaka Ikeda A & Hajime Ohigashi M. Ursolic acid: An anti- and pro-inflammatory triterpenoid. Mol. Nutr. Food Res. 2008; 52(1): 26-42.
Currier N, Solomon SE, Demicco EG & Chang D. Oncogenic Signaling Pathways Activated in DMBA-Induced Mouse Mammary Tumors. Toxicologic Pathology. 2005; 33(6): 726-737.
Majd A, Mehrabian S, Jonoobi P & Modaresi A. A Comparative Study of anti-mutation and anti-carcinogenic properties of Rosemary (Rosmarinus officinalis L.) and Lavender (Lavandula angustifolia Mill.) during their different developmental stages. Iran J Med Microbiol. 2011; 5(3): 61-67.
Lo AH, Liang YC, Lin-Shiau SY & Ho CT. Carnosol, an antioxidant in rosemary, suppresses inducible nitric oxide synthase through down-regulating nuclear factor-kappaB in mouse macrophages. Carcinogenesis. 2002; 23(6): 983-991.
Aggarwal BB, Ichikawa H, Garodia P & Weerasinghe P. From traditional Ayurvedic medicine to modern medicine: identification of therapeutic targets for suppression of inflammation and cancer. Oncologic, Endocrine & Metabolic. 2006; 10(1): 87-118.
Liang YC, Tsai SH, Tsai DC & Lin-Shiau SY. Suppression of inducible cyclooxygenase and nitric oxide synthase through activation of peroxisome proliferator-activated receptor-gamma by flavonoids in mouse macrophages. FEBS Letters. 2001;496(1): 12-8.
Serafini M, Bellocco R, Wolk A & Ekstrom AM. Total antioxidant potential of fruit and vegetables and risk of gastric cancer. Gastroenterology. 2002; 123(4): 985-91.
Cheng A, Lee M, Tsai ML & Lai CS. Rosmanol potently induces apoptosis through both the mitochondrial apoptotic pathway and death receptor pathway in human colon adenocarcinoma COLO 205 cells. Food and Chemical Toxicology. 2010; 12(3): 12-22.
Dorrie J, Sapala K & Zunino SJ. Carnosol-induced apoptosis and downregulation of Bcl-2 in B-lineage leukemia cells. Cancer Letters. 2001; 170(5): 33-39.
Huang MT, Ho CT, Wang ZY & Ho CT. Inhibition of skin tumorigenesis by rosemary and its constituents carnosol and ursolic acid. Cancer Researches. 1994; 54(3): 701-708.
Fumagalli M & et al. Strawberry tannins inhibit IL-8 secretion in a cell model of gastric inflammation. Pharmacol. Res. 2016; 111(6): 703-712.
Alarcón M, Fuentes E, Olate N, Navarrete S, Carrasco G & Palomo I. Strawberry extract presents antiplatelet activity by inhibition of inflammatory mediator of atherosclerosis (sP-selectin, sCD40L, RANTES, and IL-1β) and thrombus formation. Platelets. 2015; 26(12): 224-229.
Roomiani L, Soltani M, Akhondzadeh Basti A, Mahmoodi A, Taheri Mirghaed A & Yadollahi F. Evaluation of the chemical composition and in vitro antimicrobial activity of Rosmarinus officinalis, Zataria multiflora, Anethum graveolens and Eucalyptus globulus against Streptococcus iniae the cause of zoonotic disease in farmed fish. IJFS. 2013; 12(3): 702-16.
Alvarez-Suarez JM, Dekanski D, Ristic´ S, Radonjic´ NV & Petronijevic´ ND. Strawberry Polyphenols Attenuate Ethanol-Induced Gastric Lesions in Rats by Activation of Antioxidant Enzymes and Attenuation of MDA Increase. PLoS ONE. 2019; 6(10):
258-278.
Tong C & et al. Randomized Phase II Trial of Lyophilized Strawberries in Patients With Dysplastic Precancerous Lesions of the Esophagus. Cancer Prev Res (Phila). 2018; 5(1): 41-50.
Wang B, Han Q & Zhu Y. Oxymatrine inhibited cell proliferation by inducing apoptosis in human lung cancer A549 cells. Bio-Med Mater Eng. 2015; 26(2): 165-172.
Dikshit P, Goswami A, Mishra A, Catterjee M & Jana NR. Curcumin induces stress response, neurite outgrowth and prevent NF-κB activation by inhibiting the proteasome function. Neurotox Res. 2006; 9(1): 29-37.