Cytotoxic Effects of Rhododendron ponticum L. Extract on Prostate Carcinoma and Adenocarcinoma Cell Line (DU145, PC3)

Rhododendron species, having been used in traditional medicine for the treatment of inflammation, pain, cold, asthma, skin and gastro-intestinal disease, are distributed widely around the world. Mad honey obtained from the nectar of common rhododendron (Rhododendron ponticum L.), which is distributed throughout Black Sea region of Turkey, contains grayanotoxins, which are toxic diterpenes. The grayanotoxins, mostly grayanotoxins I and III, which are present in leaves, flowers and nectar responsible for toxicity of mad honey. The aim of this study was to investigate in vitro cytotoxic effects of the extract on prostate carcinoma cell lines. During the flowering period of common rhododendrons gathered from the Altinordu District of Ordu and dried under suitable conditions, extracted with distilled water and lyophilized. The cytotoxic activity of the extract of common rhododendron against human prostate carcinoma (DU145) and human prostate adenocarcinoma (PC3) cell lines by using the MTT and Neutral Red assay was evaluated. It was determined that the extract of common rhododendron had a dose-dependent cytotoxic effect. IC50 of the extract was found to be 283.3 and 169.9 µg/mL in MTT assay, and 307.6 and 346.0 µg/mL in Neutral Red assay for DU145 and PC3 respectively. The fact that common rhododendron has cytotoxic effects on prostate carcinoma cells suggests that it may be a potential therapeutic agent for anticarcinogenic activity.

Rhododendron ponticum L. Extractının Prostat Karsinomu ve Adenokarsinoma Hücre Hatları (DU145, PC3) Üzerindeki Sitotoksik Etkileri

Yangı, ağrı, soğuk algınlığı, astım, deri ve gastrointestinal hastalıkların tedavisinde geleneksel olarak kullanılan Ormangülü türleri (Rhododendron) dünya çapında yaygın olarak dağılım göstermektedir. Türkiye’nin Karadeniz bölgesinde dağılmış Ormangülünün (Rhododendron ponticum L.) nektarından elde edilen delibal, toksik diterpen olan grayanotoksinleri içerir. Delibalın toksisitesinden sorumlu olan grayanotoksinler, çoğunlukla grayanotoksinler I ve III, yapraklarda, çiçeklerde ve nektarlarda bulunur. Bu çalışmanın amacı, orman gülü ekstraktının prostat karsinom hücre hatları üzerine in vitro sitotoksik etkilerini araştırmaktır. Çiçeklenme döneminde Ordu Altınordu ilçesinden toplanan orman gülü, uygun koşullar altında kurutuldu, distile su ile ekstrakte ve sonrasında liyofilize edildi. İnsan prostat kanseri (DU145) ve insan prostat adenokarsinoması (PC3) hücre hatlarına karşı orman gülü ekstraktının sitotoksik etkinliği MTT ve Nötral Kırmızı testleri ile değerlendirildi. Orman gülü ekstraktının doza bağımlı bir sitotoksik etki yaptığı tespit edildi. Ekstraktın IC50’si, DU145 ve PC3 için MTT analizinde, sırasıyla 283.3 ve 169.9 µg/mL ve Nötral kırmızı analizinde, sırasıyla 307.6 ve 346.0 µg/mL olarak bulundu. Orman gülü, prostat karsinom hücreleri üzerinde sitotoksik etkilere sahip olması, antikanserojenik aktivite için potansiyel bir terapötik madde olabileceğini düşündürmektedir.

___

Esfahani M, Ataei N, Panjehpour M: Biomarkers for evaluation of prostate cancer prognosis. Asian Pac J Cancer Prev, 16 (7): 2601-2611, 2015. DOI: 10.7314/APJCP.2015.16.7.2601

Miller MA, Zachary JF: Mechanism and morphology of cellular injury, adaption, and death. In, Zachary JF (Ed): Pathologic Basic of Veterinary Disease Expert Consult. 6th edn., 11-13, Elsevier Health Sciences, 2016.

Hayes AW: Principles and methods of toxicology. 4th edn., Raven Press, New York, 2001.

Vijayarathna S, Sasidharan S: Cytotoxicity of methanol extracts of Elaeis guineensis on MCF-7 and Vero cell lines. Asian Pac J Trop Biomed, 2 (10): 826-829, 2012. DOI: 10.1016/S2221-1691(12)60237-8

Gilmour KM: Perspectives on carbonic anhydrase. Comp Biochem Physiol A Mol Integr Physiol, 157 (3): 193-197, 2010. DOI: 10.1016/j. cbpa.2010.06.161

Durdagi S, Scozzafava G, Vullo D, Sahin H, Kolayli S, Supuran CT: Inhibition of mammalian carbonic anhydrases I-XIV with grayanotoxin III: Solution and in silico studies. J Enzyme Inhib Med Chem, 29 (4): 469-475, 2014. DOI: 10.3109/14756366.2013.804072

Chen SN, Zhang HP, Wang LQ, Bao GH, Qin GW: Diterpenoids from the flowers of Rhododendron molle. J Nat Prod, 67 (11): 1903-1906, 2004. DOI: 10.1021/np040012o

ManiKumar P, Pardhu G, Ravinder S, Lakshmi V, Tejaswini K, Pradeep VB: Phytochemical screening, antimicrobial & anti proliferative properties of Rhododendron ponticum on prostate epithelial cancer cells. J Pharm Sci Res, 3 (11): 1552-1555, 2011.

Seephonkai P, Popescu R, Zehl M, Krupitza G, Urban E, Kopp B: Ferruginenes A-C from Rhododendron ferrugineum and their cytotoxic evaluation. J Nat Prod, 74 (4): 712-717, 2011. DOI: 10.1021/np100778k

Way TD, Tsai SJ, Wang CM, Ho CT, Chou CH: Chemical constituents of rhododendron formosanum show pronounced growth ınhibitory effect on non-small-cell lung carcinoma cells. J Agric Food Chem, 62 (4): 875-884, 2014. DOI: 10.1021/jf404243p

Fauzi AN, Norazmi MN, Yaacob NS: Tualang honey induces apoptosis and disrupts the mitochondrial membrane potential of human breast and cervical cancer cell lines. Food Chem Toxicol, 49 (4): 871-878, 2011. DOI: 10.1016/j.fct.2010.12.010

Cragg GM, Newman DJ: Plants as a source of anti-cancer agents. J Ethnopharmacol, 100 (1-2): 72-79, 2005. DOI: 10.1016/j.jep.2005.05.011

Stankovic MS, Curcic MG, Zizic JB, Topuzovic MD, Solujic SR, Markovic SD: Teucrium plant species as natural sources of novel anticancer compounds: Antiproliferative, proapoptotic and antioxidant properties. Int J Mol Sci, 12 (7): 4190-4205, 2011. DOI: 10.3390/ ijms12074190

Jang M, Cai L, Udeani GO, Slowing KV, Thomas CF, Beecher CWW, Fong HHS, Farnsworth NR, Kinghorn AD, Mehta RG, Moon RC, Pezzuto JM: Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science, 275 (5297): 218-220, 1997. DOI: 10.1126/science.275.5297.218

Yurdakök B, Baydan E: Cytotoxic effects of Eryngium kotschyi and Eryngium maritimum on Hep2, HepG2, Vero and U138 MG cell lines. Pharm Biol, 51 (12): 1579-1585, 2013, DOI: 10.3109/13880209.2013.803208

Byun KS, Lee YW, Jin HJ, Lee MK, Lee HY, Lee KJ, Heo MY, Yu CY, Lee JH: Genotoxicity and cytotoxicity in human cancer and normal cell lines of the extracts of Rhododendron brachycarpum D. Don leaves. Korean J Med Crop Sci, 13 (4): 199-205, 2005.

Jang GU, Choi SU, Lee KR: Cytotoxic constituents of Rhododendron brachycarpum. Yakhak Hoeji, 49 (3): 244-248, 2005.

Gündüz A, Tatlı Ö, Türedi S: Mad honey poisoning from the past to the present. Turk J Emerg Med, 8 (1): 46-49, 2008.

Bilir EK, Sevin S, Tutun H, Alcigir ME, Yarsan E: Cytotoxic and antiproliferative effects of Rhododendron ponticum L. extract on rat glioma cell line (F98). Int J Pharm Sci Res, 9 (5): 1000-1007, 2018.

Eken C: Grayanotoxin poisoning. Turk J Emerg Med, 4 (2): 76-77, 2004.

Öztaşan N, Altınkaynak K, Akçay F, Göçer F, Dane Ş: Effects of mad honey on blood glucose and lipid levels in rats with streptozocin-induced diabetes. Turk J Vet Anim Sci, 29 (5): 1093-1096, 2005.

Popescu R, Kopp B: The genus Rhododendron: An ethnopharmacological and toxicological review. J Ethnopharmacol, 147 (1): 42- 62, 2013. DOI: 10.1016/j.jep.2013.02.022

Sahin H, Turumtay EA, Yildiz O, Kolayli S: Grayanotoxin-III detection and antioxidant activity of mad honey. Int J Food Prop, 18 (12): 2665-2674, 2015. DOI: 10.1080/10942912.2014.999866

Onat FY, Yegen BC, Lawrence R, Oktay A, Oktay S: Mad honey poisoning in man and rat. Rev Environ Health, 9 (1): 3-9, 1991.

Tasdemir D, Demirci B, Demirci F, Dönmez AA, Hüsnü K, Baser C, Rüedi P: Analysis of the volatile components of five Turkish Rhododendron species by headspace solid-phase microextraction and GC-MS (HS-SPME-GC-MS). Z Naturforsch C, 58 (11-12): 797-803, 2003. DOI: 10.1515/znc-2003-11-1208

Eguaras MJ, Fuselli S, Gende L, Fritz R, Ruffinengo SR, Clemente G, Gonzalez A, Bailac PN, Ponzi MI: An in vitro evaluation of tagetes minuta essential oil for the control of the honeybee pathogens Paenibacillus larvae and Ascosphaera apis, and the parasitic mite varroa destructor. J Essent Oil Res, 17 (3): 336-340, 2005. DOI: 10.1080/10412905.2005. 9698924

Sütlüpinar N, Mat A, Satganoğlu Y: Poisoning by toxic honey in Turkey. Arch Toxicol, 67 (2): 148-150, 1993.

Koca I, Koca AF: Poisoning by mad honey: A brief review. Food Chem Toxicol, 45 (8): 1315-1318, 2007. DOI: 10.1016/j.fct.2007.04.006

Demir S, Turan I, Aliyazicioglu Y: Selective cytotoxic effect of Rhododendron luteum extract on human colon and liver cancer cells. J BUON, 21 (4): 883-888, 2016.

Usta A, Yayli B, Kahriman N, Alpay Karaoglu S, Yayli N: Composition and antimicrobial activity of essential oil from the flower of Rhododendron luteum sweet. Asian J Chem, 24 (5): 1927-1930, 2012.

Eşen D, Zedaker SM, Kirwan JL, Mou P: Soil and site factors influencing purple-flowered rhododendron (Rhododendron ponticum L.) and eastern beech forests (Fagus orientalis Lipsky) in Turkey. For Ecol Manage, 203 (1- 3): 229-240, 2004. DOI: 10.1016/j.foreco.2004.07.052

Irving E, Hebda R: Concerning the origin and distribution of rhododendrons. JARS, 47 (3): 1-17, 1993.

Milne RI, Abbott RJ: Origin and evolution of invasive naturalized material of Rhododendron ponticum L. in the British Isles. Mol Ecol, 9 (5): 541-556, 2000. DOI: 10.1046/j.1365-294x.2000.00906.x
Kafkas Üniversitesi Veteriner Fakültesi Dergisi-Cover
  • ISSN: 1300-6045
  • Yayın Aralığı: Yılda 6 Sayı
  • Başlangıç: 1995
  • Yayıncı: Kafkas Üniv. Veteriner Fak.
Sayıdaki Diğer Makaleler

Deneysel Rat Modeli: Anestezi İndüksiyonu Öncesi %100 O2 İle Preoksijenizasyon Uygun mu Değil mi?

Buket DEMİRCİ, Erdem ÖZKISACIK, Varlik K. EREL, Tugba OZBEK CELIK, Mustafa YILMAZ

Antibiotic Resistance of Salmonella spp. Isolated from Raw Chicken Wings

NEBAHAT BİLGE, LEYLA VATANSEVER, ÇİĞDEM SEZER

Çin’in Fujian Eyaletinde Domuz Parvovirus 7 (PPV7) İzolatlarının Genetik Karakterizasyonu

Ru-Jing CHEN, Ting-Ting LAI, Qiu-Yong CHEN, Xue-Min WU, Yong-Liang CHE, Chen-Yan WANG, Lun-Jiang ZHOU, Long-Bai WANG, Shan YANG

Yumurta Tavuğu Yemlerinde Solvent Ekstrakte Aspir Küspesinin Soya Yağı İle Birlikte Kullanımının Performans, Yumurta Kalitesi ve Yumurta Sarısı Yağ Asitleri Kompozisyonu Üzerine Etkileri

Engin YENİCE, Meltem GÜLTEKİN, Barış ERTEKİN, Züleyha KAHRAMAN

In vitro Model of the Blood-brain Barrier Established by Co-culture of Primary Sheep Cerebral Microvascular Endothelial and Astrocyte Cells

Jingjing REN, Mingwei YANG, Genqiang YAN, Jianjun JIANG, Pengyan WANG

Immunological and Antistreptococcal Effects of Salvia officinalis and Aloe vera Extracts Supplemented Feed in Rainbow Trout (Oncorhynchus mykiss)

Ali Akbar TAFI, Saeed MESHKINI, Amir TUKMECHI, Mojtaba ALISHAHI, Farzaneh NOORI

Analysis of Expressed Genes in Normal and Tumoral Mammary Gland Tissue of the Terrier Dog

Nehir OZDEMIR OZGENTURK, Zehra OMEROGLU ULU, Salih ULU, Merve ÇELİK, Burçin TELLİOĞLU, FUNDA YILDIRIM, IRAZ AKIŞ AKAD, Aydın GÜREL, CEMAL ÜN, KEMAL ÖZDEM ÖZTABAK

Düzenli ve Yoğun Egzersiz Yaptırılan Ratlarda Takviye Olarak Tüketilen Dallı Zincirli Amino Asitlerin Miyokard ve Koroner Damarlar Üzerine Etkisi

Mahmut YESİN, İbrahim RENCÜZOĞULLARI, Metin ÇAĞDAŞ, Fatih MEDETALİBEYOĞLU, Uğur AYDIN, Doğan İLİŞ, Ekin Emre ERKILIÇ, Yasemen ADALI, Yavuz KARABAĞ, İnanç ARTAÇ, Süleyman KARAKOYUN

Presence and Antibiotic Resistance of Listeria monocytogenes in Raw Milk and Dairy Products

AKSEM AKSOY, ÇİĞDEM SEZER, LEYLA VATANSEVER, GÜVEN GÜLBAZ

Primer Koyun Serebral Mikrodamar Endotelyal ve Astrosit Hücrelerinin Birlikte Kültüre Edilmesiyle Oluşturulmuş In vitro Kan Beyin Bariyeri Modeli

Jingjing REN, Mingwei YANG, Genqiang YAN, Jianjun JIANG, Pengyan WANG