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.
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 andgastro-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 toxicditerpenes. The grayanotoxins, mostly grayanotoxins I and III, which are present in leaves, flowers and nectar responsible for toxicityof mad honey. The aim of this study was to investigate in vitro cytotoxic effects of the extract on prostate carcinoma cell lines. Duringthe 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 prostatecarcinoma (DU145) and human prostate adenocarcinoma (PC3) cell lines by using the MTT and Neutral Red assay was evaluated. Itwas determined that the extract of common rhododendron had a dose-dependent cytotoxic effect. IC50 of the extract was found tobe 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 thatcommon rhododendron has cytotoxic effects on prostate carcinoma cells suggests that it may be a potential therapeutic agent foranticarcinogenic activity.
___
- 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