Yıllanmış Sarımsak Ekstraktlarının Miyeloid Kanser Hücre Serisi Üzerine Apoptotik Etkileri
Year 2021,
Volume: 10 Issue: 3, 513 - 520, 23.09.2021
Sevil Cengiz
,
Meltem Uçar
,
Orhan Değer
,
Fahri Uçar
,
Asuman Yiğit Gerigelmez
Abstract
Sarımsak (Allium sativum) yüzyıllar boyunca gerek çeşni ve gerekse medikal amacıyla kullanılan bir baharattır. Yapılan çalışmalarla antibakteriyel, antiviral, antiinflamatuar, antifungal, antimutajenik, antioksidan, antialerjik, yaşlanmayı azaltıcı, antitümoral ve immünositimülatör aktiviteleri olduğu belirlenmiştir. Kaspaz-3’ün aktifleşmesi kaspaz aktifleşme zincirini başlatarak apoptozu gerçekleştirir. Bu çalışmada DMSO’lu yıllanmış sarımsak ekstraktlarının (AGE) Miyoid Kanser Hücre hatları üzerine (HL-60) apoptotik etkisi belirlenmesi amaçlandı. İnsan lenfosit hücreleri kontrol grup olarak kullanılarak akış sitometrisi yöntemi ve spektrofotometrik kaspaz-3 aktivitesi analizleri kullanıldı. HL-60 hücre hatlarına üzerine en yüksek apoptotik etki 12,5 mg /mL konsantrasyondaki yıllanmış sarımsak ekstraktlarınında gözlendi (%10,9). Lenfosit hücrelerine göre HL-60 hücre hatlarındaki kaspaz-3 aktivitesi ise 1,28 ile 3,02 kat oranında arttığı tespit edildi. Yıllanmış sarımsak ekstraktlarının HL-60 hücre hatlarında kaspaz-3'ün aktivitesini arttırarak apoptozu tetiklediği sonucuna ulaşıldı. Sarımsağın yaşlandırılmasının antikanser etkisi olduğu ve bu konuda ilave çalışmaların kanser tedavisine yeni bakış açıları kazandırabileceği düşünülmektedir.
Supporting Institution
KTÜ BAP
Project Number
Project Number: 114.001.14
Thanks
Danışman Hocam Merhum Prof. Dr. Ekin ÖNDER'e Teşekkür Ederim.
References
- Jamshidi-Kia, F, Lorigooini, Z. and Amini-Khoei, H. (2018). “Medicinal Plants: Past History and Future Perspective”. J Herbmed Pharmacol. 7 (1), 1-7.
- Ayaz, E. and Alpsoy, H.C. (2007). “Garlic (Allium sativum) and Traditional Medicine”. 31(2). 145-149.
- Lawson, L.D. and Gardner, C.D. (2005). “Composition. Stability. And Bioavailability Of Garlic Products Being Used In A Clinical Trial”. J Agric Food Chem, 53 (16), 6254–6261.
- Vinson, J.A, Su, X, Zubik, L. and Bose, P. (2001). “Phenol Antioxidant Quantity And Quality In Foods: Fruits”. J Agric Food Chem, 49, 5315-5321.
- Iciek, M, Inga-Kwiecien, I. and Lidia Włodek, L. (2009). “Biological Properties of Garlic And Garlic-Derived Organosulfur Compounds”. Environmental And Molecular Mutagenesis, 50, 247-265.
- Hiyasat, B, Sabha, D, Grotzinger, K, Kempfert, J, Rauwald, J.W, Mohr, F.W. and Dhein. S. (2009). “Antiplatelet Activity of Allium Ursinum And Allium Sativum”. Pharmacology, 83 (4), 197-204.
- Nouroz, F, Mehboob, M, Noreen, S, Zaidi, F. and Mobin. T. (2015). “A Review On Anticancer Activities of Garlic (Allium Sativum L.)”. Middle-East Journal of Scientific Research, 23 (6), 1145-1151.
- Guercio, V, Galeone, C, Turati, F. and La Vecchia, C. (2014). “Gastric Cancer And Allium Vegetable Intake: A Critical Review of The Experimental And Epidemiologic Evidence”. Nutrition and Cancer, 66, 757-773.
- Gonzalez, C.A, Travier, N, Lujan-Barroso, L. and Castellsague, X. et al. (2011). “Dietary Factors and In Situ and Invasive Cervical Cancer Risk In The European Prospective Investigation İnto Cancer and Nutrition Study”. International Journal Of Cancer Journal International Du Cancer, 129, 449-459.
- Galeone, C, Pelucchi, C, Dal Maso, L. and Negri, E, Montella, M, Zucchetto, A, Talamini, R and Vecchia, CL. (2009). “Allium Vegetables Intake And Endometrial Cancer Risk”. Public Health Nutrition, 12, 1576-1579.
- Omar, S.H. and Al-Wabel, N.A. (2010). “Organosulfur Compounds And Possible Mechanism Of Garlic In Cancer”. Saudi Pharm J, 18 (1), 51-58.
- Susan, E. (2007). “Apoptosis: A Review Of Programmed Cell Death”. Toxicol Pathol, 35 (4), 495-516.
- Porter, A.G. and Jänicke, R.U. (1999). “Emerging Roles of Caspase-3 in Apoptosis”. Cell Death Differ, 6 (2), 99-104.
- Liu, L, Chen, X, Hao, L, Zhang, G, Jin, Z, Li, C, Yang, Y, Rao, J. and Chen, B. (2020). “Traditional Fermented Soybean Products: Processing. Flavor Formation. Nutritional and Biological Activities’’. Crit. Rev. Food Sci. Nutr, 1-19.
- Ting, A. and Morris, P.J. (1971). “A Technique For Lymphocyte Preparation From Stored Heparinized Blood”. Vox Sang, 20 (6), 561-3.
- Tan, L, Jia, H, Liu, R, Wu, J, Han, H, Zuo, Y, Yang, S. and Huang, W. (2009). “Inhibition of NF-қB In Fusogenic Membrane Glycoprotein Causing HL-60 Cell Death: Implications For Acute Myeloid Leukemia". Cancer Lett, 273, 114- 121.
- Gorczyca, W, Melamed, M.R. and Darzynkiewicz, Z. (1998). “Analysis of Apoptosis By Flow Cytometry. In: Jaroszeski M.J. Heller R. (eds) Flow Cytometry Protocols. Methods in Molecular Biology™. vol 91. Humana Press. Totowa. NJ, 91, 217-238.
- Uçar, M, Değer, O, Gerigelmez, A.Y, Cengiz, S, Barlak, Y. and Ovalı. E. (2016). “Effect of Turkish Pollen And Propolis Extracts On Caspase-3 Activity İn Myeloid Cancer Cell Lines”. Tropical Journal of Pharmaceutical Research, 15 (11), 2445-2449.
- Takashima, M, Kanamori, Y, Kodera, Y, Morihara, N. and Tamura, K. (2017). “Aged Garlic Extract Exerts Endothelium-Dependent Vasorelaxant Effect On Rat Aorta By Increasing Nitric Oxide Production”. Phytomedicine, 24, 56–61.
- Szychowski, K.A, Rybczynska-Tkaczyk, K, Gawel-Beben, K, Swieca, M, Karas, M, Jakubczyk, A. and Gminski, J. (2018). “Characterization of Active Compounds of Different Garlic (Allium sativum L.) Cultivars”. Pol. J. Food Nutr. Sci, 68, 73–81.
- Yun, H.M, Ban, J.O, Park, K.R, Le, C.K, Jeong, H.S, Han, SB. and Hong. JT. (2014). “Potential Therapeutic Effects of Functionally Active Compounds İsolated From Garlic”. Pharmacol Ther, 14, 183-195.
- Cao, H.X, Zhu, K.X, Fan, J.G. and Qiao, L. (2014). “Garlic-Derived Allyl Sulfides In Cancer Therapy”. Anticancer Agents Med. Chem, 14, 793-799.
- Kodali, R.T. and Eslick, G.D. (2015). “Meta-analysis: Does Garlic İntake Reduce Risk Of Gastric Cancer?” Nutr. Cancer, 67, 1–11.
- Bom, J, Gunutzmann, P, Hurtado, E.C.P. and Maragno-Correa, J.M.R, Kleep, SR. and Lallo, MA. (2014). “Long-Term Treatment With Aqueous Garlic And/Or Tomato Suspensions Decreases Ehrlich Ascites tumors. Evid. Based Complement”. Altern Med, 381649.
- Milner, J.A. (2001). A Historical Perspective on Garlic and Cancer. Journal of Nutrition. 131:1027-1031.
- Fukushima, S, Takada, N, Wanibuchi, H, Hori, T, Min, W, Wanibuchi, H. and Yamamoto, S. (2001). “Suppression Of Chemical Carcinogenesis By Water-Soluble Organosulfur Compounds”. Journal of Nutrition, 131, 1049-1053.
- Greenblatt, D.J, Leigh-Pemberton, R.A. and Von Moltke, L.L. (2006).“In Vitro Interactions of Water-Soluble Garlic Components With Human Cytochromes P450”. J. Nutr, 136, 806-809.
- Dirsh, V.M, Gerbes, A.L. and Volmar, P.M. (1998). “Ajoene. A compound of Garlic Induces Apoptosis In Human Promyeloleukemik Cells. Accompanied By Generation Of Reactive Oxygen Species And Activation of Nuclear FactorKb". Molecular Pharmocology, 53, 402-407.
- Kwon, K.B, Yoo, S.J, Ryu, D.G, Yang, J.Y, Rho, H.W, Kim. J.S, Park, J.W, Kim, H. and Park, B.H.I. (2002). “Induction of Apoptosis By Diallyl Disulfıde Through Activation of Caspase-3 In Human Leukemia HL-60 cells. Biochemical Pharmacology, 63, 41-47.
- Balasenthil, S, Rao, K.S. and Nagini, S. (2002). “Garlic Induces Apoptosis During 7.12-Dimethylbenz[A]Anthracene-Induced Hamster Buccal Pouch Carcinogenesis”. Oral Oncology, 38, 431-436.
- Lamm, D.L. and Riggs, D.R. (2001). “Enhanced Immunocompetence By Garlic: Role In Bledder Cancer And Other Malignancies”. Journal of Nutrition, 131, 1067-1070.
- De Greef, D, Barton, E.M, Sandberg, E.N, Croley, C.R, Pumarol, J, Wong, T.L, Das, N. and Bishayee, A. (2020). “Anticancer potential of garlic and its bioactive constituents: a systematic and comprehensive review”. Sem. Cancer Biol, 73, 219-264
- Oommen, S, Anto, R.J, Srinivas, G. and Karunagaran, D. (2004). “Allicin (From Garlic) Induces Caspase-Mediated Apoptosis In Cancer Cells”. Eur J Pharmacol, 485 (1-3), 97-103.
- Gore, G.G, Satish, S, Ganpule, A, Sangeeta Srivastava, S. and Athavale, M. (2021). International Journal of Herbal Medicine, 9(1), 93-99
- Su, C.C, Chen, G.W, Tani, T.W, Lin, J.G. and Chung, J.G. (2006). “Crude Extract Of Garlic Induced Caspase-3 Gene Expression Leading To Apoptosis In Human Colon Cancer Cells”. In Vivo, .20 (1), 85-90.
- Iciek, M, Kwiecień, I, Chwatko, G, Sokołowska-Jeżewicz, M. Danuta, KM. and Rokita. H. (2012). “The Effects O f Garlic-Derived Sulfur Compounds On Cell Proliferation. Caspase 3 Activity. Thiol Levels And Anaerobic Sulfur Metabolism İn Human Hepatoblastoma HepG2 Cells”. Cell Biochem Funct,.30 (3), 198-204.
- Knowles, L.M. and Milner, J.A. (2001). “Possible Mechanism By Which Allyl Sulfides Suppress Neoplastic Cell Proliferation”. J Nutr, 131 (3), 1061-1066.
- Srivastava, S.K, Hu, X, Xia, H, Zaren, H.A, Chattercje, M.L, Agarwal, R. and Singh, S.V. (1997). “Mechanism of Differential Efficacy of Garlic Organosulfıdes In Preventing Benzo(A)Pyrene-Induced Cancer In Mice”. Cancer Letters, 118, 61-67.
- Cerell, C, Dicato, M, Jacob, C. and Diederich, M. (2011). “Chemical Properties And Mechanisms Determining The Anti-Cancer Action Of Garlic-Derived Organic Sulfur Compounds.Anti-Cancer Agents İn Medicinal Chemistry (Formerly Current Medicinal Chemistry Anti-Cancer Agents ) ”. Bentham Science Publishersvolüme, 11 (3), 267-271.
- Amarakoon, S. and Jayasekara, D. (2017). “A Review on Garlic (Allium Sativum L.) As A Functional Food. Journal of Pharmacognosy And Phytochemistry, 6 (6), 1777-1780.
Effects of Aged Garlic Extracts On Caspase-3 Activity In Myeloid Cancer Cell Lines
Year 2021,
Volume: 10 Issue: 3, 513 - 520, 23.09.2021
Sevil Cengiz
,
Meltem Uçar
,
Orhan Değer
,
Fahri Uçar
,
Asuman Yiğit Gerigelmez
Abstract
Garlic (Allium sativum) is a spice used for centuries for both condiment and medicinal purposes. Studies have shown that it has antibacterial, antiviral, anti-inflammatory, antifungal, antimutagenic, antioxidant, antiallergic, anti-aging, antitumoral and immunostimulatory activities. Activation of caspase-3 initiates the caspase activation chain, leading to apoptosis. In this study aimed to determine the apoptotic effect of DMSO-containing aged garlic extracts (AGE) on Myoid Cancer Cell lines (HL-60). Flow cytometry method and spectrophotometric caspase-3 activity analyzes were used using human lymphocyte cells as a control group. The highest apoptotic effect on HL-60 cell lines was observed in aged garlic extracts at a concentration of 12.5 mg/mL (10.9%). It was determined that caspase-3 activity in HL-60 cell lines increased by 1.28 to 3.02 times compared to lymphocyte cells. It was concluded that aged garlic extracts triggered apoptosis by increasing the activity of caspase-3 in HL-60 cell lines. It is thought that the aging of garlic has an anticancer effect and additional studies on this subject may bring new perspectives to cancer treatment.
Project Number
Project Number: 114.001.14
References
- Jamshidi-Kia, F, Lorigooini, Z. and Amini-Khoei, H. (2018). “Medicinal Plants: Past History and Future Perspective”. J Herbmed Pharmacol. 7 (1), 1-7.
- Ayaz, E. and Alpsoy, H.C. (2007). “Garlic (Allium sativum) and Traditional Medicine”. 31(2). 145-149.
- Lawson, L.D. and Gardner, C.D. (2005). “Composition. Stability. And Bioavailability Of Garlic Products Being Used In A Clinical Trial”. J Agric Food Chem, 53 (16), 6254–6261.
- Vinson, J.A, Su, X, Zubik, L. and Bose, P. (2001). “Phenol Antioxidant Quantity And Quality In Foods: Fruits”. J Agric Food Chem, 49, 5315-5321.
- Iciek, M, Inga-Kwiecien, I. and Lidia Włodek, L. (2009). “Biological Properties of Garlic And Garlic-Derived Organosulfur Compounds”. Environmental And Molecular Mutagenesis, 50, 247-265.
- Hiyasat, B, Sabha, D, Grotzinger, K, Kempfert, J, Rauwald, J.W, Mohr, F.W. and Dhein. S. (2009). “Antiplatelet Activity of Allium Ursinum And Allium Sativum”. Pharmacology, 83 (4), 197-204.
- Nouroz, F, Mehboob, M, Noreen, S, Zaidi, F. and Mobin. T. (2015). “A Review On Anticancer Activities of Garlic (Allium Sativum L.)”. Middle-East Journal of Scientific Research, 23 (6), 1145-1151.
- Guercio, V, Galeone, C, Turati, F. and La Vecchia, C. (2014). “Gastric Cancer And Allium Vegetable Intake: A Critical Review of The Experimental And Epidemiologic Evidence”. Nutrition and Cancer, 66, 757-773.
- Gonzalez, C.A, Travier, N, Lujan-Barroso, L. and Castellsague, X. et al. (2011). “Dietary Factors and In Situ and Invasive Cervical Cancer Risk In The European Prospective Investigation İnto Cancer and Nutrition Study”. International Journal Of Cancer Journal International Du Cancer, 129, 449-459.
- Galeone, C, Pelucchi, C, Dal Maso, L. and Negri, E, Montella, M, Zucchetto, A, Talamini, R and Vecchia, CL. (2009). “Allium Vegetables Intake And Endometrial Cancer Risk”. Public Health Nutrition, 12, 1576-1579.
- Omar, S.H. and Al-Wabel, N.A. (2010). “Organosulfur Compounds And Possible Mechanism Of Garlic In Cancer”. Saudi Pharm J, 18 (1), 51-58.
- Susan, E. (2007). “Apoptosis: A Review Of Programmed Cell Death”. Toxicol Pathol, 35 (4), 495-516.
- Porter, A.G. and Jänicke, R.U. (1999). “Emerging Roles of Caspase-3 in Apoptosis”. Cell Death Differ, 6 (2), 99-104.
- Liu, L, Chen, X, Hao, L, Zhang, G, Jin, Z, Li, C, Yang, Y, Rao, J. and Chen, B. (2020). “Traditional Fermented Soybean Products: Processing. Flavor Formation. Nutritional and Biological Activities’’. Crit. Rev. Food Sci. Nutr, 1-19.
- Ting, A. and Morris, P.J. (1971). “A Technique For Lymphocyte Preparation From Stored Heparinized Blood”. Vox Sang, 20 (6), 561-3.
- Tan, L, Jia, H, Liu, R, Wu, J, Han, H, Zuo, Y, Yang, S. and Huang, W. (2009). “Inhibition of NF-қB In Fusogenic Membrane Glycoprotein Causing HL-60 Cell Death: Implications For Acute Myeloid Leukemia". Cancer Lett, 273, 114- 121.
- Gorczyca, W, Melamed, M.R. and Darzynkiewicz, Z. (1998). “Analysis of Apoptosis By Flow Cytometry. In: Jaroszeski M.J. Heller R. (eds) Flow Cytometry Protocols. Methods in Molecular Biology™. vol 91. Humana Press. Totowa. NJ, 91, 217-238.
- Uçar, M, Değer, O, Gerigelmez, A.Y, Cengiz, S, Barlak, Y. and Ovalı. E. (2016). “Effect of Turkish Pollen And Propolis Extracts On Caspase-3 Activity İn Myeloid Cancer Cell Lines”. Tropical Journal of Pharmaceutical Research, 15 (11), 2445-2449.
- Takashima, M, Kanamori, Y, Kodera, Y, Morihara, N. and Tamura, K. (2017). “Aged Garlic Extract Exerts Endothelium-Dependent Vasorelaxant Effect On Rat Aorta By Increasing Nitric Oxide Production”. Phytomedicine, 24, 56–61.
- Szychowski, K.A, Rybczynska-Tkaczyk, K, Gawel-Beben, K, Swieca, M, Karas, M, Jakubczyk, A. and Gminski, J. (2018). “Characterization of Active Compounds of Different Garlic (Allium sativum L.) Cultivars”. Pol. J. Food Nutr. Sci, 68, 73–81.
- Yun, H.M, Ban, J.O, Park, K.R, Le, C.K, Jeong, H.S, Han, SB. and Hong. JT. (2014). “Potential Therapeutic Effects of Functionally Active Compounds İsolated From Garlic”. Pharmacol Ther, 14, 183-195.
- Cao, H.X, Zhu, K.X, Fan, J.G. and Qiao, L. (2014). “Garlic-Derived Allyl Sulfides In Cancer Therapy”. Anticancer Agents Med. Chem, 14, 793-799.
- Kodali, R.T. and Eslick, G.D. (2015). “Meta-analysis: Does Garlic İntake Reduce Risk Of Gastric Cancer?” Nutr. Cancer, 67, 1–11.
- Bom, J, Gunutzmann, P, Hurtado, E.C.P. and Maragno-Correa, J.M.R, Kleep, SR. and Lallo, MA. (2014). “Long-Term Treatment With Aqueous Garlic And/Or Tomato Suspensions Decreases Ehrlich Ascites tumors. Evid. Based Complement”. Altern Med, 381649.
- Milner, J.A. (2001). A Historical Perspective on Garlic and Cancer. Journal of Nutrition. 131:1027-1031.
- Fukushima, S, Takada, N, Wanibuchi, H, Hori, T, Min, W, Wanibuchi, H. and Yamamoto, S. (2001). “Suppression Of Chemical Carcinogenesis By Water-Soluble Organosulfur Compounds”. Journal of Nutrition, 131, 1049-1053.
- Greenblatt, D.J, Leigh-Pemberton, R.A. and Von Moltke, L.L. (2006).“In Vitro Interactions of Water-Soluble Garlic Components With Human Cytochromes P450”. J. Nutr, 136, 806-809.
- Dirsh, V.M, Gerbes, A.L. and Volmar, P.M. (1998). “Ajoene. A compound of Garlic Induces Apoptosis In Human Promyeloleukemik Cells. Accompanied By Generation Of Reactive Oxygen Species And Activation of Nuclear FactorKb". Molecular Pharmocology, 53, 402-407.
- Kwon, K.B, Yoo, S.J, Ryu, D.G, Yang, J.Y, Rho, H.W, Kim. J.S, Park, J.W, Kim, H. and Park, B.H.I. (2002). “Induction of Apoptosis By Diallyl Disulfıde Through Activation of Caspase-3 In Human Leukemia HL-60 cells. Biochemical Pharmacology, 63, 41-47.
- Balasenthil, S, Rao, K.S. and Nagini, S. (2002). “Garlic Induces Apoptosis During 7.12-Dimethylbenz[A]Anthracene-Induced Hamster Buccal Pouch Carcinogenesis”. Oral Oncology, 38, 431-436.
- Lamm, D.L. and Riggs, D.R. (2001). “Enhanced Immunocompetence By Garlic: Role In Bledder Cancer And Other Malignancies”. Journal of Nutrition, 131, 1067-1070.
- De Greef, D, Barton, E.M, Sandberg, E.N, Croley, C.R, Pumarol, J, Wong, T.L, Das, N. and Bishayee, A. (2020). “Anticancer potential of garlic and its bioactive constituents: a systematic and comprehensive review”. Sem. Cancer Biol, 73, 219-264
- Oommen, S, Anto, R.J, Srinivas, G. and Karunagaran, D. (2004). “Allicin (From Garlic) Induces Caspase-Mediated Apoptosis In Cancer Cells”. Eur J Pharmacol, 485 (1-3), 97-103.
- Gore, G.G, Satish, S, Ganpule, A, Sangeeta Srivastava, S. and Athavale, M. (2021). International Journal of Herbal Medicine, 9(1), 93-99
- Su, C.C, Chen, G.W, Tani, T.W, Lin, J.G. and Chung, J.G. (2006). “Crude Extract Of Garlic Induced Caspase-3 Gene Expression Leading To Apoptosis In Human Colon Cancer Cells”. In Vivo, .20 (1), 85-90.
- Iciek, M, Kwiecień, I, Chwatko, G, Sokołowska-Jeżewicz, M. Danuta, KM. and Rokita. H. (2012). “The Effects O f Garlic-Derived Sulfur Compounds On Cell Proliferation. Caspase 3 Activity. Thiol Levels And Anaerobic Sulfur Metabolism İn Human Hepatoblastoma HepG2 Cells”. Cell Biochem Funct,.30 (3), 198-204.
- Knowles, L.M. and Milner, J.A. (2001). “Possible Mechanism By Which Allyl Sulfides Suppress Neoplastic Cell Proliferation”. J Nutr, 131 (3), 1061-1066.
- Srivastava, S.K, Hu, X, Xia, H, Zaren, H.A, Chattercje, M.L, Agarwal, R. and Singh, S.V. (1997). “Mechanism of Differential Efficacy of Garlic Organosulfıdes In Preventing Benzo(A)Pyrene-Induced Cancer In Mice”. Cancer Letters, 118, 61-67.
- Cerell, C, Dicato, M, Jacob, C. and Diederich, M. (2011). “Chemical Properties And Mechanisms Determining The Anti-Cancer Action Of Garlic-Derived Organic Sulfur Compounds.Anti-Cancer Agents İn Medicinal Chemistry (Formerly Current Medicinal Chemistry Anti-Cancer Agents ) ”. Bentham Science Publishersvolüme, 11 (3), 267-271.
- Amarakoon, S. and Jayasekara, D. (2017). “A Review on Garlic (Allium Sativum L.) As A Functional Food. Journal of Pharmacognosy And Phytochemistry, 6 (6), 1777-1780.