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 durumdaameliyatsız tedaviler ön plana çıkmaktadır. Hypericum perforatum (HP)/ Sarı Kantaron bitkisi halk arasında yüzyıllardır pek çokhastalığın tedavisinde kullanılmaktadır. Bu çalışmada, HP bitkisinin insan BCC hücreleri üzerindeki etkisinin ve molekülermekanizmasının aydınlatılması amaçlanmıştır. Yöntemler: İnsan BHK hücre hatları TE 354.T, ATCC®'den elde edildi. Daha sonra Dulbecco Modifiye Eagle ortamında kültiveedildi. BHK hücreleri, her bir flaskta (n = 12) 2x106 hücre konsantrasyonunda üretildi. İnkübasyondan sonra, flasklardan 6'sına48 saat boyunca %0.8 HP ekstresi ve % 99.2 medyum ile uygulanırken, kontrol grubuna herhangi bir uygulama yapılmadı. HP'ninBHK kanser hücrelerinde mitokondriyal aracılı intrinsik ve ekstrinsik apoptotik yolak ajanları, hücre döngüsü G2 / M kontrolnoktası kinaz ve inflamatuar mediyatörler üzerindeki etkileri araştırıldı. Her iki gruptaki mediatörlerin ekspresyonu veaktiviteleri ELISA testi ile değerlendirildi. Bulgular: HP ekstresi tedavisinin BHK hücre hatlarında, apoptotik proteinlerin (AIF, GADD153, GRP78, kaspaz-3, Bax) ve hücredöngüsü G2 / M kontrol noktası kinazının (Wee1) ekspresyonunu arttırdığı, buna karşılık antiapoptotik proteini (Bcl-2) veinflamatuar mediatörleri (iNOS, COX-2, cPLA2, NFkB) azalttığı belirlendi. Sonuç: HP ekstresi, apoptotik, antiinflamatuvar ve anti-kanser etkisi ile BHK’da rutin kemoterapiyi destekleyebilir ve BHKtedavisinde kemoterapötik ilaçlara direnci azaltmada bir umut ışığı olabilir.

Apoptotic and Anti-inflammatory Effects of Hypericum Perforatum Extract inHuman 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.

___

  • 1. Kim DP, Kus KJB, Ruiz E. Basal Cell Carcinoma Review. Hematol Oncol Clin North Am. 2019; 33: 13-24.
  • 2. Patočka J. The chemistry, pharmacology, and toxicology of the biologically active constituents of the herb Hypericum perforatum L. J Appl Biomed. 2003; 1: 61-70.
  • 3. Hışıl Y, Şahin F, Omay SB. Composition of Hypericum perforatum L. and its medical importance. Int J Hematol Oncol. 2005; 15: 212-8.
  • 4. Colasanti A, Kisslinger A, Liuzzi R, et al. Hypericin Photosensitization of Tumor and Metastatic Cell Lines of Human Prostate. J Photochem Photobiol B. 2000; 54: 103-7.
  • 5. Lu HF, Chie YJ, Yang MS, et al. Apigenin Induces Caspase-Dependent Apoptosis in Human Lung Cancer A549 Cells Through Bax- And Bcl-2-triggered Mitochondrial Pathway. Int J Oncol. 2010; 36: 1477- 84.
  • 6. Pistritto G, Trisciuoglio D, Ceci C, Gafuri A, D’Orazi G. Apoptosis as anticancer mechanism: function and dysfunction of its modulators and targeted therapeutic strategies. Aging (Albany NY). 2016; 8: 603-19.
  • 7. Alimbetov D, Askarova S, Umbayev B, Davis T, Kipling D. Pharmacological Targeting of Cell Cycle, Apoptotic and Cell Adhesion Signaling Pathways Implicated in Chemoresistance of Cancer Cells. Int J Mol Sci. 2018; 19: 1690.
  • 8. Kim C, Kim B. Anti-Cancer Natural Products and Their Bioactive Compounds Inducing ER Stress-Mediated Apoptosis: A Review. Nutrients. 2018; 10: 1021.
  • 9. Berköz M, Allahverdiyev O, Yıldırım M. Investigation of the effect of hyperforin and hypericin on inflammatory response in RAW 264.7 macrophages. Van Med J. 2018; 25: 124-31.
  • 10. Orhan IE, Kartal M. LC-DAD-MS-assisted quantification of marker compounds in Hypericum perforatum L. (St. John's wort) and its antioxidant activity. Turk J Pharmaceut Sci. 2015; 12: 279-86.
  • 11. Ferguson A, Morris C, Curley J. Hypericum perforatum Extracts and Hypericin Treatment of a Mouse Mammary Cancer Cell Line Induces Growth Inhibition in a Dose Dependent Manner. J Exp Second Sci. 2012; 1: 14-8.
  • 12. Mosmann T. Rapid colorometric assay for cellular growth and survival: Application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65: 55- 63.
  • 13. Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976; 72: 248-54.
  • 14. Yildirim IH, Azzawri AA, Duran T. Thymoquinone induces apoptosis via targeting the Bax/BAD and Bcl-2 pathway in breast cancer cells. Dicle Med J. 2019; 46: 411-7.
  • 15. Wong RS. Apoptosis in cancer: from pathogenesis to treatment. J Exp Clin Cancer Res. 2011; 30: 87.
  • 16. Hashemi Goradel N, Najafi M, Salehi E, Farhood B, Mortezaee K. Cyclooxygenase-2 in cancer: A review. J Cell Physiol. 2019; 234: 5683-99.
  • 17. Niknami M, Patel M, Witting PK, Dong Q. Molecules in focus: cytosolic phospholipase A2-alpha. Int J Biochem Cell Biol. 2009; 41: 994-7.
  • 18. Todoric J, Antonucci L, Karin M. Targeting Inflammation in Cancer Prevention and Therapy. Cancer Prev Res (Phila). 2016; 9: 895-905.
  • 19. Yazıcı P, Alizadehshargh S, Güner Akdoğan G. Apoptosis: Regulatory Molecules, Its Relationship with Diseases and Apoptosis Detection Methods: Review. Turkiye Klinikleri J Med Sci. 2009; 29: 1677-86.
  • 20. Kale J, Osterlund EJ, Andrews DW. BCL-2 family proteins: changing partners in the dance towards death. Cell Death Differ. 2018; 25: 65-80.
  • 21. Kleemann B, Loos B, Scriba TJ, Lang D, Davids LM. St John's Wort (Hypericum perforatum L.) Photomedicine: Hypericin-Photodynamic Therapy Induces Metastatic Melanoma Cell Death. PLoS One. 2014; 9: e103762.
  • 22. Merhi F, Tang R, Piedfer M, et al. Hyperforin Inhibits Akt1 Kinase Activity and Promotes Caspase-Mediated Apoptosis Involving Bad and Noxa Activation in Human Myeloid Tumor Cells. PLoS One. 2011; 6: e25963.
  • 23. Martarelli D, Martarelli B, Pediconi D, et al. Hypericum Perforatum Methanolic Extract Inhibits Growth of Human Prostatic Carcinoma Cell Line Orthotopically Implanted in Nude Mice. Cancer Lett. 2004; 210: 27-33.
  • 24. Di Carlo G, Nuzzo I, Capasso R, et al. Modulation of apoptosis in mice treated with Echinacea and St. John's wort. Pharmacol Res. 2003; 48: 272-7.
  • 25. Jang MH, Lee TH, Shin MC, et al. Protective Effect of Hypericum Perforatum Linn (St. John's Wort) Against Hydrogen Peroxide-Induced Apoptosis on Human Neuroblastoma Cells. Neurosci Lett. 2002; 329: 177- 80.
  • 26. Yegani AA, Istifli ES, Tekeli IO, Sakin F, Kaplan HM. Proapoptotic Effect of Hypericum perforatum (St. John's Wort) Extract in Human Colorectal Adenocarcinoma Cell Line HT29. Int J Pharmacol. 2020; 16: 120-5.
Dicle Tıp Dergisi-Cover
  • ISSN: 1300-2945
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 1963
  • Yayıncı: Cahfer GÜLOĞLU
Sayıdaki Diğer Makaleler

COVID-19 and Other Viral Pneumonias

Nazlı GÖRMELİ KURT, Melih ÇAMCI

Management of Adults With Suspected Foreign Body Aspiration

Efsun UĞUR, Elif TANRIVERDİ, Demet TURAN, Binnaz YILDIRIM, Şeyma YILMAZ, İrfan CHOUSEİN, Mehmet Akif ÖZGÜL, Erdoğan ÇETİNKAYA

İleri Evre Medüller Tiroid Kanseri Tedavisinde Tirozin Kinaz İnhibitörü Kullanımı-Tek Merkez Deneyimi

Senar EBINC, Zeynep ORUÇ, Zuhat URAKÇI, Muhammet Ali KAPLAN, Mehmet KÜÇÜKÖNER, Abdurrahman IŞIKDOĞAN

Comparison of hematological inflammatory parameters in patients with exfoliative glaucoma and exfoliative syndrome

Atılım Armağan DEMİRTAŞ, Mine KARAHAN

Mutation Analysis of Beta-Thalassemia Major Patients and Their Parents in Diyarbakir Province, Turkey

Cemal POLAT, Nuriye METE, Murat SÖKER

The reasons for conversion from laparoscopic appendectomy to open surgery in children: the first experience on 100 cases in a single

Ali Erdal KARAKAYA, AHMET GÖKHAN GÜLER, Ahmet Burak DOĞAN, Fatih YAZAR

Servikal ve Jeneralize Distonide Periferik Sessiz Periyot

Melih TÜTÜNCÜ, Hikmat ABBASZADE, Ayşegül GÜNDÜZ, Meral E. KIZILTAN

Optimal Tedavi, Altmış Beş Yaş ve Üstü Glioblastome Multiforme Tanılı Hastalarda Sağkalım Üzerine Etkili mi?

Atike Gökçen DEMİRAY, Arzu YAREN, Burcu YAPAR TASKÖYLÜ, Serkan DEĞİRMENCİOĞLU, Gamze GÖKÖZ DOĞU

Hyaluronik Asitin Endometrium Dokusunda αVβ3 İntegrin ve Metalloproteinaz Ekspresyonuna Etkisi

Hatice ORUÇ DEMİRBAĞ, Nazlı ÇİL, Gülçin ABBAN METE, Semih TAN

Karotis Arter Darlığı ile Birlikte Sınır Zonu İnfarktı Saptanan Olguların Klinik ve Radyolojik Özellikleri ile Karotis Arter Stentlemesinin Erken Dönem Sonuçları

Hasan Hüseyin KOZAK, Hasan Hüseyin KIR, Ahmet BUĞRUL, Osman KOÇ