ZEYTİN KARASUYU FENOLİKLERİNDEN 3,4-DİHİDROKSİFENİL ETANOLÜN FARKLI PROSTAT KANSERİ HÜCRE HATLARINDAKİ SİTOTOKSİK ETKİLERİ

Zeytinyağı üretimi sırasında oluşan yan ürünlerden zeytin karasuyunun zengin fenolik içeriği ve buna bağlı olarak antioksidan, antitrombotik, antiinflamasyon, hipokolesterolemik, antimikrobiyal, antiviral ve antikanserojenik aktiviteleri bilimsel çalışmalarla ortaya konmuştur. Zeytin karasuyunun temel bileşenlerinden biri 3,4-dihidroksifenil etanol (3,4-DHPEA)’dür. 3,4-DHPEA’nın birçok kanser tipi üzerinde antikanserojenik etkileri araştırılmasına rağmen prostat kanseri üzerindeki etkilerini irdeleyen çalışmalar literatürde sınırlı sayıdadır. Bu amaçla çalışmamızda, 3,4-DHPEA’nın orijin, genetik yapı ve karakteristik özellikler bakımından farklı 5 insan prostat kanseri hücre hatları üzerindeki benzer ve farklı sitotoksik etkileri araştırılmıştır. 3,4-DHPEA farklı konsantrasyonlarda prostat kanseri hücre hatları (LNCaP, C4-2, 22Rv1, PC3 ve DU-145) üzerinde 72 saate kadar uygulandı ve hücre canlılıkları Cell TiterGlo luminesan testi uygulanarak belirlendi. Tüm deneyler 3 paralel yapıldı ve 3 kere tekrarlandı. Sonuçlar varyans analizi (ANOVA) ile karşılaştırıldı ve %5’den düşük olasılıklar (P

CYTOTOXIC EFFECTS OF 3,4-DIHYDROXYPHENYL ETHANOL, AN OLIVE MILL WASTE WATER PHENOLIC, ON DIFFERENT PROSTATE CANCER CELL LINES

The rich phenolic content of olive mill waste water obtained as by-product during olive oil production and its antioxidant, antithrombotic, anti-inflammatory, hypocholesterolemic, antimicrobial, antiviral, and anticancerogenic activities have been revealed by scientific studies. One of the main components of olive oil is 3,4-dihydroxyphenyl ethanol (3,4-DHPEA). Although the effect of 3,4- DHPEA was studied on many types of cancer, studies on prostate cancer are limited in the literature. For this purpose, similar and different cytotoxic effects of 3,4-DHPEA on 5 human prostate cancer cell lines differing in origin, genetic structure, and characteristic features were investigated. The 3,4-DHPEA was applied on prostate cancer cell lines (LNCaP, C4-2, 22Rv1, PC3, and DU-145) at different concentrations for up to 72 hours and cell viabilities were measured by the Cell Titer-Glo luminescence assay. All experiments were performed in 3 parallel and repeated 3 times. Results were compared with analysis of variance (ANOVA) and the probabilities less than 5% (P

___

  • Artajo, L.S., Romero, M.P., Morelló, J.R., Motilva, M.J. (2006). Enrichment of refined olive oil with phenolic compounds: Evaluation of their antioxidant activity and their effect on the bitter index. Journal of Agricultural and Food Chemistry, 54(16), 6079-6088.
  • Aruoma, O.I., Deiana, M., Jenner, A., Halliwell, B., Kaur, H., Banni, S., Corongiu, F.P., Assunta Dessi, M., Aeschbach, R. (1998). Effect of hydroxytyrosol found in extra virgin olive oil on oxidative DNA damage and on low-density lipoprotein oxidation. Journal of Agricultural and Food Chemistry, 46(12), 5181-5187.
  • Bono, A.V. (2004). Overview of current treatment strategies in prostate cancer. European Urology Supplements, 3(1), 2-7.
  • Bouaziz, M., Grayer, R.J., Simmonds, M.S.J., Damak, M., Sayadi, S. (2005). Identification and antioxidant potential of flavonoids and low molecular weight phenols in olive cultivar Chemlali growing in Tunisia. Journal of Agricultural and Food Chemistry, 53(2), 236-241.
  • Cansino Alcaide, J.R., Martínez-Piñeiro, L. (2006). Molecular biology in prostate cancer. Clinical and Translational Oncology, 8(3), 148-152.
  • Capasso, R., Evidente, A., Schivo, L., Orru, G., Marcialis, M.A., Cristinzio, G. (1995). Antibacterial polyphenols from olive oil mill waste waters. Journal of Applied Microbiology, 79(4), 393-398.
  • Cardinali, A., Linsalata, V., Lattanzio, V., Ferruzzi, M.G. (2011). Verbascosides from olive mill waste water: assessment of their bioaccessibility and intestinal uptake using an in vitro digestion/Caco-2 model system. Journal of Food Science, 76(2), H48-54.
  • Fabiani, R., De Bartolomeo, A., Rosignoli, P., Servili, M., Montedoro, G.F., Morozzi, G. (2002). Cancer chemoprevention by hydroxytyrosol isolated from virgin olive oil through G1 cell cycle arrest and apoptosis. European Journal of Cancer Prevention, 11, 351-358.
  • Fabiani, R., Rosignoli, P., De Bartolomeo, A., Fuccelli, R., Servili, M., Montedoro, G.F., Morozzi, G. (2008). Oxidative DNA damage is prevented by extracts of olive oil, hydroxytyrosol, and other olive phenolic compounds in human blood mononuclear cells and HL60 cells. Journal of Nutrition, 138(8), 1411-1416.
  • Fabiani, R., Sepporta, M.V., Rosignoli, P., De Bartolomeo, A., Crescimanno, M., Morozzi, G. (2012). Antiproliferative and pro-apoptotic activities of hydroxytyrosol on different tumour cells: The role of extracellular production of hydrogen peroxide. European Journal of Nutrition, 51(4), 455-464.
  • Fki, I., Allouche, N., Sayadi, S. (2005). The use of polyphenolic extract, purified hydroxytyrosol and 3,4-
  • dihydroxyphenyl acetic acid from olive mill wastewater for the stabilization of refined oils: A potential alternative to synthetic antioxidants. Food Chemistry, 93(2), 197-204.
  • Facchini, A., Cetrullo, S., D’Adamo, S., Guidotti, S., Minguzzi, M., Facchini, A., Borzì, R.M., Flamigni, F. (2014). Hydroxytyrosol prevents increase of osteoarthritis markers in human chondrocytes treated with hydrogen peroxide or growth-related oncogene α. PLoS ONE, 9(10), 1-9.
  • Ibarra, A., Sniderman, Z. (2008). Olive polyphenol concentrate. US patent application 20080014322 A1 Jan 17th. US patent application.
  • Luo, C., Li, Y., Wang, H., Cui, Y., Feng, Z., Li, H., Li, Y., Wang, Y., Wurtz, K., Weber, P., Long, J., Liu, J. (2013). Hydroxytyrosol promotes superoxide production and defects in autophagy leading to anti-proliferation and apoptosis on human prostate cancer cells. Current Cancer Drug Targets, 13(6), 625-639.
  • Orenay Boyacioglu, S. (2018). Role of PTEN in modulating preventive effect of 3,4-DHPEA against oxidative stress. Erciyes University Journal of Health Sciences, 27(1), 48-54.
  • Quiles, J.L., Farquharson, A.J., Simpson, D.K., Grant, I., Wahle, K.W.J. (2002). Olive oil phenolics: effects on DNA oxidation and redox enzyme mRNA in prostate cells. The British Journal of Nutrition, 88(3), 225-234; discussion 223-224.
  • Rosignoli, P., Fuccelli, R., Sepporta, M.V., Fabiani, R. (2016). In vitro chemo-preventive activities of hydroxytyrosol: The main phenolic compound present in extra-virgin olive oil. Food & Function, 7(1), 301- 307.
  • Sepporta, M.V., López-García, M.Á., Fabiani, R., Maya, I., Fernández-Bolaños, J.G. (2013). Enhanced chemopreventive activity of hydroxytyrosol on HL60 and HL60R cells by chemical conversion into thio derivatives. European Journal of Pharmaceutical Sciences, 48(4-5), 790-798.
  • Siegel, R.L., Miller, K.D., Jemal, A. (2016). Cancer statistics. CA: A Cancer Journal for Clinicians, 66(1), 7-30.
  • Soler-Rivas, C., Espín, J.C., Wichers, H.J. (2000). Oleuropein and related compounds. Journal of the Science of Food and Agriculture, 80, 1013-1023.
  • Sousa, A., Ferreira, I.C.F.R., Calhelha, R., Andrade, P.B., Valentão, P., Seabra, R., Estevinho, L., Bento, A., Pereira, J.A. (2006). Phenolics and antimicrobial activity of traditional stoned table olives “alcaparra”. Bioorganic & Medicinal Chemistry, 14(24), 8533- 8538.
  • Warleta, F., Quesada, C.S., Campos, M., Allouche, Y., Beltrán, G., Gaforio, J.J. (2011). Hydroxytyrosol protects against oxidative DNA damage in human breast cells. Nutrients, 3(10), 839-857.
  • Zhou, C.K., Check, D.P., Lortet-Tieulent, J., Laversanne, M., Jemal, A., Ferlay, J., Bray, F., Cook, M.B., Devesa, S.S. (2016). Prostate cancer incidence in 43 populations worldwide: An analysis of time trends overall and by age group. International Journal of Cancer, 138(6), 1388-1400.
  • Zubair, H., Bhardwaj, A., Ahmad, A., Srivastava, S.K., Khan, M.A., Patel, G.K., Singh, S., Singh, A.P. (2017). Hydroxytyrosol induces apoptosis and cell cycle arrest and suppresses multiple oncogenic signaling pathways in prostate cancer cells. Nutrition and Cancer, 69(6), 932-942.