Eray Metin GÜLER, Hatice HİRA, Hümeyra KALELİ, Abdurrahim KOÇYİĞİT

Dialil Disülfit ve Dialil Trisülfit’in İnsan Prostat Kanser Hücreleri Üzerine Sitotoksik, Genotoksik ve Apoptotik Etkileri

Amaç: Kanser dünya çapında artan bir sağlık sorunu olup, erkeklerde en sık görülen kanser türü olan prostat kanseri, birçok ülke için ikinci ölüm nedenidir. Kanser tedavisinde konvansiyonel yöntemlerin başarısız olması nedeni ile doğal etken maddelerin kullanımı son yıllarda giderek daha fazla ilgi görmektedir. Bu çalışmanın amacı, Sarımsak (Allium sativum) etken maddelerinden olan, Dialil Disülfit (DADS) ve Dialil Trisülfit’in (DATS) farklı konsantrasyonlarının insan prostat kanser hücreleri üzerine sitotoksik, genotoksik ve apoptotik etkilerini araştırmaktır.Materyal ve Metot: Bu çalışmada prostat kanser (PC-3) ve sağlıklı prostat epitel hücrelerine (WPMY-1) DADS ve DATS’ın sitotoksik etkisi luminometrik ATP testiyle, genotoksik etkisi alkalen tekli hücre jel elektroforez (Comet Assay) yöntemiyle, apoptotik etkisi akridin turuncusu/etidyum bromür yöntemiyle ölçüldü. Ayrıca, mitokondriyal membran potansiyeli (MMP), hücre içi kalsiyum (Ca2+) ve reaktif oksijen türlerinin (ROS) seviyeleri farklı florometrik yöntemlerle ve glutatyon seviyeleri ise luminometrik yöntem ile tayin edildi. Bulgular: DADS ve DATS doza bağımlı olarak hem kanser hem de normal hücrelerde glutatyon ve MMP seviyelerini anlamlı şekilde düşürürken, sitotoksisite, DNA hasarı, apoptoz, hücre içi Ca2+ ve ROS düzeylerini anlamlı derecede arttırmıştır. Ayrıca, DATS’ın kanser hücreleri üzerine sitotoksik, genotoksik ve apoptotik etkileri sağlıklı hücrelere ve DADS’a göre daha yüksek bulunmuştur.Sonuç: Bulgular, hem DADS hem de DATS’ın prostat kanseri hücrelerinde doza bağlı bir şekilde sitotoksik, genotoksik ve apoptotik etkilere sahip olduğunu ve DATS’ın DADS’a göre daha etkili olduğunu göstermiştir. Bu nedenle, DATS’ın prostat kanseri tedavisi için kullanılabilecek seçeneklerden biri olabileceğini önermekteyiz.

Anahtar Kelimeler:

Prostat kanseri, dialil disülfit, dialil trisülfit, kanser tedavisi

Cytotoxic, Genotoxic and Apoptotic Effects of Diallyl Disulfide and Diallyl Trisulfide on Human Prostate Cancer Cells

AbstractBackground: Cancer is an increasing health problem worldwide; however, prostate cancer is the most common cancer in men and the second leading cause of death in many countries. Due to the failure of conventional methods in the treatment of cancer, the use of natural active ingredients in cancer treatment has gained increasing attention in recent years. The aim of this study is to investigate cytotoxic, genotoxic, and apoptotic effects of different concentrations of diallyl disulfide (DADS) and diallyl trisulfide (DATS) on human prostate cancer cells.Methods: In this study, the cytotoxic effect of DADS and DATS in prostate cancer (PC-3) and healthy prostate epithelial cells (WPMY-1) was measured by luminometric ATP test, the genotoxic effect was measured by alkaline single-cell electrophoresis (Comet Assay) method, and apoptotic effect by acridine orange/ethidium bromide method. In addition, mitochondrial membrane potential (MMP), intracellular calcium (Ca2+), and reactive oxygen species (ROS) levels were measured by different fluorometric methods, and glutathione levels were determined by the luminometric method.Results: DADS and DATS reduced statistically significantly glutathione and MMP levels while increased cytotoxicity, DNA damage, apoptosis, intracellular Ca2+, and ROS levels in both cancer and healthy cells dose-dependent manner. In addition, the cellular effects of DATS were higher than DADS in cancer cells than healthy cells.Conclusions: The findings showed that both DADS and DATS have a dose-dependent cytotoxic, genotoxic and apoptotic effect in prostate cancer cells and that DATS is more effective than DADs. Therefore, we suggest that DATS may be one of the options available for the treatment of prostate cancer.

Keywords:

Prostate cancer, diallyl disulfide, diallyl trisulfide, cancer treatment,

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