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Prostat Ve Akciğer Kanseri Hücre Hatlarinda Rosmarinus Officinalis L

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Prostat Ve Akciğer Kanseri Hücre Hatlarinda Rosmarinus Officinalis L PROSTAT VE AKCİĞER KANSERİ HÜCRE HATLARINDA ROSMARİNUS OFFİCİNALİS L. (BİBERİYE) EKSTRESİNİN SİTOTOKSİK ETKİLERİNİN ARAŞTIRILMASI Buse VATANSEVER T.C. ULUDAĞ ÜNİVERSİTESİ FEN BİLİMLERİ ENSTİTÜSÜ PROSTAT VE AKCİĞER KANSERİ HÜCRE HATLARINDA ROSMARİNUS OFFİCİNALİS L. (BİBERİYE) EKSTRESİNİN SİTOTOKSİK ETKİLERİNİN ARAŞTIRILMASI Buse VATANSEVER Prof. Dr. Hulusi MALYER YÜKSEK LİSANS TEZİ BİYOLOJİ ANABİLİM DALI BURSA-2014 Her Hakkı Saklıdır TEZ ONAYI Buse VATANSEVER tarafından hazırlanan “Prostat ve akciğer kanseri hücre hatlarında Rosmarinus officinalis L. (biberiye) ekstresinin sitotoksik etkilerinin araştırılması” adlı tez çalışması aşağıdaki jüri tarafından oy birliği/oy çokluğu ile Uludağ Üniversitesi Fen Bilimleri Enstitüsü Biyoloji Anabilim Dalı’nda YÜKSEK LİSANS TEZİ olarak kabul edilmiştir. Danışman : Prof. Dr. Hulusi MALYER Başkan : Prof. Dr. Hulusi MALYER Uludağ Üniversitesi Fen Edebiyat Fakültesi Biyoloji Anabilim Dalı Üye : Prof. Dr. Hale ŞAMLI Uludağ Üniversitesi Veteriner Fakültesi Genetik Anabilim Dalı Üye : Doç. Dr. Sevcan ÇELENK Uludağ Üniversitesi Fen Edebiyat Fakültesi Biyoloji Anabilim Dalı Yukarıdaki sonucu onaylarım Prof. Dr. Ali Osman DEMİR Enstitü Müdürü ../../…. U.Ü. Fen Bilimleri Enstitüsü, tez yazım kurallarına uygun olarak hazırladığım bu tez çalışmasında; -tez içindeki bütün bilgi ve belgeleri akademik kurallar çerçevesinde elde ettiğimi, -görsel, işitsel ve yazılı tüm bilgi ve sonuçları bilimsel ahlak kurallarına uygun olarak sunduğumu, -başkalarının eserlerinden yararlanılması durumunda ilgili eserlere bilimsel normlara uygun olarak atıfta bulunduğumu, -atıfta bulunduğum eserlerin tümünü kaynak olarak gösterdiğimi, -kullanılan verilerde herhangi bir tahrifat yapmadığımı, -ve bu tezin herhangi bir bölümünü bu üniversite veya başka bir üniversitede başka bir tez çalışması olarak sunmadığımı beyan ederim. 13/08/2014 Buse VATANSEVER ÖZET Yüksek Lisans Tezi PROSTAT VE AKCİĞER KANSERİ HÜCRE HATLARINDA ROSMARİNUS OFFİCİNALİS L. (BİBERİYE) EKSTRESİNİN SİTOTOKSİK ETKİLERİNİN ARAŞTIRILMASI Buse VATANSEVER Uludağ Üniversitesi Fen Bilimleri Enstitüsü Biyoloji Anabilim Dalı Danışman: Prof. Dr. Hulusi MALYER Bu çalışmada, Türkiye'de doğal olarak yetişen Rosmarinus officinalis L. (biberiye) bitkisinin farklı çözücüler (etanol ve su) ile hazırlanmış ekstrelerinin prostat ve akciğer kanseri hücre hatları (VCaP ve Calu-1) üzerindeki sitotoksik aktiviteleri araştırılmıştır. Bu amaçla, ilk basamak olan in vitro sitotoksisiteyi belirlemede kullanılan WST-1 ve SRB canlılık testlerinden faydalanılmıştır. Ayrıca hücrelerdeki sitotoksik aktivite, gerçek zamanlı sitotoksisite analiz sistemi (xCELLigence RTCA) ile doğrulanmıştır. Rosmarinus officinalis L. bitkisinden elde edilen etanol ekstresinin VCaP ve Calu-1 hücreleri üzerinde infüzyon ekstresine kıyasla daha güçlü bir sitotoksik etkiye neden olduğu bulunmuştur. Bu çalışmanın sonuçlarından yola çıkarak bir sonraki inceleme basamağının, kullanılan ekstrelerin kanser tedavisindeki büyüme baskılayıcı etkisinden sorumlu olan etken maddelerin araştırılması olduğu sonucuna varılmıştır. Anahtar Kelimeler: Prostat kanseri, akciğer kanseri, Rosmarinus officinalis, biberiye, sitotoksisite 2014, xii + 144 sayfa. i ABSTRACT MSc Thesis THE INVESTIGATION OF CYTOTOXIC EFFECTS OF ROSMARINUS OFFICINALIS L. (ROSEMARY) EXTRACT ON THE PROSTATE AND LUNG CANCER CELL LINES Buse VATANSEVER Uludag University Graduate School of Natural and Applied Sciences Department of Biology Supervisor: Prof. Dr. Hulusi MALYER In this study, cytotoxic activity of extracts (ethanol and water) of Rosmarinus officinalis L., (rosemary) naturally a plant grown in Turkey, is tested against prostate and lung cancer cell lines (VCaP and Calu-1). For this purpose, WST-1 and SRB cell viability tests are utilized to determine in vitro cytotoxicity. Furthermore, cytotoxic activity is confirmed with real time cytotoxicity analysis system (xCELLigence RTCA). It has been found that ethanol extracts of Rosmarinus officinalis L. more powerful cytotoxic activity compared to water extracts on VCaP and Calu-1 cells. Based on results of this study, it has been concluded that a subsequent step of examination is investigation of active agents, being responsible for growth inhibitory effect of the extracts in the treatment of cancer. Keywords: Prostate cancer, lung cancer, Rosmarinus officinalis, rosemary, cytotoxicity 2014, xii + 144 pages. ii TEŞEKKÜR Yüksek lisans eğitimimin düzenli işleyişi için büyük bir özveri gösteren, her konuda ilgi ve desteğini benden esirgemeyen, öneri ve eleştirileriyle beni daima yönlendiren tez danışmanım değerli hocam Sayın Prof. Dr. Hulusi MALYER'e, Tez konumun bulunması, planlanması ve çalışmamın yürütülmesi süresince her aşamada bilgi ve tecrübelerini benimle paylaşan, çalışma alanımla ilgili deneyim kazanmamı sağlayan, her zaman ilgi, anlayış ve desteğini gördüğüm, yanında çalışmaktan onur duyduğum değerli hocam Sayın Prof. Dr. Hale ŞAMLI'ya, Tez çalışmam süresince Veteriner Fakültesi Genetik Anabilim Dalına ait Hücre Kültürü Laboratuvarını kullanabilme olanağı sağlayan ve her zaman değerli fikir ve önerilerinden faydalandığım hocam Sayın Prof. Dr. Faruk BALCI'ya, Laboratuvar çalışmalarımda ve deneysel sonuçları yorumlamamda değerli görüş ve deneyimlerinden yararlandığım ve yakın ilgilerini hiç esirgemeyen hocam Sayın Doç. Dr. Ferda ARI'ya, Tez çalışmamın her aşamasında bilgi birikimlerini tüm içtenliği ile paylaşan, destek ve yardımları ile her konuda yanımda olan ve bana yol gösteren Sayın Dr. Zeynep Özlem ŞIĞVA'ya, Çalışmamda yer alan bitkinin ekstraksiyon aşamasındaki yardımlarından dolayı, Sayın Prof. Dr. Gülendam TÜMEN'e, Sayın Doç. Dr. Serap ÇELİKLER KASIMOĞULLARI'na ve Sayın Arş. Gör. Mehmet SARIMAHMUT'a, tez çalışmamda hücre hatlarından faydalandığım Sayın Prof. Dr. Cumhur GÜNDÜZ'e, Yüksek lisans eğitimim boyunca tecrübelerinden ve yardımlarından faydalandığım, ilgi ve desteklerini hiçbir zaman esirgemeyen hocalarım Sayın Prof. Dr. Adem BIÇAKCI'ya, Sayın Doç. Dr. Sevcan ÇELENK'e, Sayın Araş. Gör. Dr. Aycan TOSUNOĞLU'na ve Sayın Öğr. Gör. Gülşah SAATÇIOĞLU'na, Tez çalışmam boyunca bana her konuda yardımcı olan, benden moral ve desteklerini esirgemeyen ve birlikte çalışmaktan çok büyük keyif aldığım arkadaşlarım Nazlıhan AZTOPAL'a ve Burak ÖZDEMİR'e, Eğitimimin her aşamasında maddi ve manevi desteklerini benden esirgemeyen, hayatım boyunca hiçbir fedakârlıktan kaçınmayıp her zaman yanımda olan ve aldığım her kararda beni destekleyen, bugünlere gelmemde en büyük emeğin sahibi ve başarılarımın esin kaynağı sevgili ''AİLEM''e, sonsuz teşekkürü bir borç bilirim. Bu tez çalışması Uludağ Üniversitesi Bilimsel Araştırma Projeleri Komisyonu Başkanlığı (HDP(V)-2014/5) numaralı proje tarafından desteklenmiştir. Buse VATANSEVER 13/08/2014 iii İÇİNDEKİLER Sayfa ÖZET.................................................................................................................................. i ABSTRACT ...................................................................................................................... ii TEŞEKKÜR ..................................................................................................................... iii SİMGELER ve KISALTMALAR DİZİNİ ...................................................................... vi ŞEKİLLER DİZİNİ ........................................................................................................ viii ÇİZELGELER DİZİNİ .................................................................................................... xi 1. GİRİŞ ............................................................................................................................ 1 2. KAYNAK ÖZETLERİ ................................................................................................. 3 2.1. Kanser ........................................................................................................................ 3 2.1.1. Karsinogenez süreci ................................................................................................ 5 2.1.2. Kanser hücrelerinin özellikleri .............................................................................. 10 2.1.3. Hücre döngüsü ve kanser ...................................................................................... 12 2.2. Prostat Kanseri ......................................................................................................... 19 2.2.1. Prostat kanserinin görülme sıklığı ......................................................................... 20 2.2.2. Prostat kanseri risk faktörleri ................................................................................ 22 2.3. Akciğer Kanseri ....................................................................................................... 24 2.3.1. Akciğer kanserinin görülme sıklığı ....................................................................... 27 2.3.2. Akciğer kanseri risk faktörleri .............................................................................. 29 2.4. Rosmarinus officinalis L. (Biberiye) ........................................................................ 32 2.4.1. Lamiaceae (Labiatae, Ballıbabagiller) familyası hakkında genel bilgiler ............ 34 2.4.2. Rosmarinus officinalis L.'in sistematikteki yeri .................................................... 35 2.4.3. Rosmarinus officinalis L.'in genel özellikleri ve yayılış alanları .......................... 36 2.4.4. Rosmarinus officinalis L.'in kimyasal kompozisyonu ve biyolojik aktiviteleri .... 39 2.5. Prostat ve Akciğer
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