Ebru CELIK, Halil Mahir KAPLAN, Ergin ŞİNGİRİK, Muhammed Salih ÇELİK, Harun ALP

Apoptotic and Anti-inflammatory Effects of Hypericum Perforatum Extract in Human Basal Cell Carcinoma TE 354.T Cell Line

Objectives: Basal cell carcinoma is the most common malignancy in in the Caucasian race and is a serious health problem with its ever-increasing incidence and high cost. Although the treatment is surgical, some elderly patients do not accept surgical intervention. In this case, non-surgical treatments come into prominence. The Hypericum perforatum (HP) / St. John's Wort plant has been used in the treatment of many diseases for centuries among local people. Here, we aimed to aimed to elucidate the effect and molecular mechanism of the HP plant on BCC cells. Methods: Human BCC cell lines TE 354.T were acquired from ATCC®, then were cultured in Dulbecco's Modified Eagle's Medium. BCC cells were seeded at a concentration of 2x106cells in each flask (n=12). After incubation, while six of the flasks were applied with a 0.8% HP extract and 99.2% medium for 48 hours, no application was made to the control group. The effects of HP on mitochondrial mediated intrinsic and extrinsic apoptotic pathway agents, cell cycle G2 / M checkpoint kinases and inflammatory mediators were investigated in BCC cancer cells. The expression and activities of these mediators in both groups were evaluated by ELISA test. Results: It was determined that HP extract treatment increased the expression of apoptotic proteins (AIF, GADD153, GRP78, caspase-3, Bax) and cell cycle G2 / M checkpoint kinase (Wee1), though it reduced antiapoptotic protein (Bcl-2) and inflammatory mediators (iNOS, COX-2, cPLA2, NFkB) in BCC cell lines. Conclusion: HP extract can support routine chemotherapy on BCC cells with its apoptotic, anti-inflammatory and anti-cancer effect, and may be a beacon of hope in reducing resistance to chemotherapeutic drugs in the treatment of BCC.

İnsan Bazal Hücreli Karsinom TE 354.T Hücre Hattında Hypericum Perforatum Ekstraktının Apoptotik ve Antiinflamatuvar Etkileri

Amaç: Bazal hücreli karsinom (BHK), beyaz ırkta en sık görülen malignitedir ve sürekli artan insidansı ve yüksek maliyeti ile ciddi bir sağlık problemidir. Tedavisi cerrahi olsa da bazı yaşlı hastalar cerrahi müdahaleyi kabul etmemektedirler. Bu durumda ameliyatsız tedaviler ön plana çıkmaktadır. Hypericum perforatum (HP)/ Sarı Kantaron bitkisi halk arasında yüzyıllardır pek çok hastalığın tedavisinde kullanılmaktadır. Bu çalışmada, HP bitkisinin insan BCC hücreleri üzerindeki etkisinin ve moleküler mekanizmasının aydınlatılması amaçlanmıştır. Yöntemler: İnsan BHK hücre hatları TE 354.T, ATCC®'den elde edildi. Daha sonra Dulbecco Modifiye Eagle ortamında kültive edildi. BHK hücreleri, her bir flaskta (n = 12) 2x106 hücre konsantrasyonunda üretildi. İnkübasyondan sonra, flasklardan 6'sına 48 saat boyunca %0.8 HP ekstresi ve % 99.2 medyum ile uygulanırken, kontrol grubuna herhangi bir uygulama yapılmadı. HP'nin BHK kanser hücrelerinde mitokondriyal aracılı intrinsik ve ekstrinsik apoptotik yolak ajanları, hücre döngüsü G2 / M kontrol noktası kinaz ve inflamatuar mediyatörler üzerindeki etkileri araştırıldı. Her iki gruptaki mediatörlerin ekspresyonu ve aktiviteleri ELISA testi ile değerlendirildi. Bulgular: HP ekstresi tedavisinin BHK hücre hatlarında, apoptotik proteinlerin (AIF, GADD153, GRP78, kaspaz-3, Bax) ve hücre döngüsü G2 / M kontrol noktası kinazının (Wee1) ekspresyonunu arttırdığı, buna karşılık antiapoptotik proteini (Bcl-2) ve inflamatuar mediatörleri (iNOS, COX-2, cPLA2, NFkB) azalttığı belirlendi. Sonuç: HP ekstresi, apoptotik, antiinflamatuvar ve anti-kanser etkisi ile BHK’da rutin kemoterapiyi destekleyebilir ve BHK tedavisinde kemoterapötik ilaçlara direnci azaltmada bir umut ışığı olabilir.

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