COMPARISON OF THE EFFECTS OF DOCETAXEL and AMYGDALIN TREATMENT ON CELL DEATH, INTEGRIN-α and INTEGRIN-β EXPRESSIONS IN DU145 PROSTATE CANCER CELL LINE

Year 2024, , 420 - 428, 21.10.2024

Çiğdem Karaca , Evrim Suna Arıkan Söylemez , Esra Aslan , Fatma Fırat , Zafer Söylemez

https://doi.org/10.18229/kocatepetip.1402118

Abstract

OBJECTIVE: Prostate cancer (PC) ranks second among cancer-related deaths in men, and most deaths are caused by metastasis. Integrins, which are cell surface receptors, play an important role in cancer metastasis. It has been shown that integrin alpha2beta1 expression is effective in cell adhesion, migration, and invasion by increasing binding to collagen I in metastatic PCs. Docetaxel chemotherapy is used in PC, but it is ineffective in advanced stages. Amygdalin is a cyanogenic glycoside commonly found in fruit seeds, there is conflict in the literature regarding its effectiveness in cancer treatment. We aimed to compare the effects of Amygdalin and Docetaxel treatments on the DU145 prostate cancer cell line on integrinalfa2 (ITGA2) and integrinbeta1 (ITGB1) expressions, as well as their effects on cell death, Caspase-3, and Beclin-1.
MATERIAL AND METHODS: Propagated DU145 cells were divided into four groups. Amygdalin was given to the first group, Docetaxel was given to the second group, and Amygdalin andDocetaxel were given together to the third group. They were exposed to the active substances for 24 hours. The fourth group (Control) was not given any substance. mRNA levels of ITGA2 and ITGB1 genes were determined by the Real-time PCR method. Caspase-3 and Beclin-1 staining were performed immunocytochemically to evaluate cell death.
RESULTS: There was an increase in ITGA2 and ITGB1 expressions in the groups administered by Amygdalin and by Docetaxel (P<0.05). The decrease in ITGB1 expression was significant in the group given Amygdalin+Docetaxel (P<0.001). Caspase-3 (P<0.05) and Beclin-1 (P<0.05) immunoreactivities were observed to increase in all three groups compared to the control group.
CONCLUSIONS: It was observed that Docetaxel increased cell death more than Amygdalin in DU145 PC cells, and when Amygdalin and Docetaxel were used together, ITGA2 and ITGB1 expressions were significantly reduced. Our results suggest that dual treatment of Amygdalin and Docetaxel may prevent prostate cancer metastases.

Keywords

Amygdalin, Docetaxel, Prostate cancer, Integrin alpha2beta1.

Project Number

19.TIP.013

DU145 PROSTAT KANSERİ HÜCRE HATTINDA DOSETAKSEL ve AMİGDALİN TEDAVİSİNİN HÜCRE ÖLÜMÜ, İNTEGRİN-α ve İNTEGRİN-β EKSPRESYONLARI ÜZERİNDEN ETKİLERİNİN KARŞILAŞTIRILMASI

Abstract

AMAÇ: Prostat kanseri (PK) erkeklerde kansere bağlı ölümler arasında ikinci sırada yer almaktadır ve ölümlerin çoğu metastaz kaynaklıdır. Kanser metastazında hücre yüzey reseptörleri olan integrinler önemli rol oynarlar. İntegrin alfa2beta1’in metastatik prostat kanserlerinde kollajen I’e bağlanmayı artırarak hücre adezyon, migrasyon ve invazyonunda etkili olduğu gösterilmiştir. Prostat kanserinde Dosetaksel kemoterapisi kullanılmakta fakat ileri evrelerde bu tedavi etkisiz kalmaktadır. Amigdalin meyve tohumlarında yaygın olarak bulunan siyanojenik bir glikozittir ve kanser tedavisinde kullanımı konusunda literatürde çelişkiler bulunmaktadır. Çalışmamızda Amigdalin ve Dosetaksel tedavilerinin DU145 prostat kanseri hücre hattına olan etkilerini integrinalfa2 (ITGA2) ve integrinbeta1 (ITGB1) ekspresyonları, ayrıca hücre ölümü üzerine olan etkilerini Caspase-3 ve Beclin-1 üzerinden karşılaştırmayı amaçladık.
GEREÇ VE YÖNTEM: DU145 hücreleri çoğaltılarak dört gruba ayrıldı. Birinci gruba Amygdalin, ikinci gruba Dosetaksel, üçüncü gruba Amygdalin ve Dosetaksel birlikte verilerek 24 saat boyunca aktif maddelere maruz bırakıldı. Dördüncü gruba (Kontrol) herhangi bir madde verilmedi. ITGA2 ve ITGB1 genlerinin mRNA düzeyleri Real-Time PCR yöntemiyle belirlendi. Hücre ölümünü değerlendirmek için immünositokimyasal olarak Caspase-3 ve Beclin-1 boyamaları yapıldı.
BULGULAR: Amigdalin, Dosetaksel uygulanan gruplarda ITGA2 ve ITGB1 ekspresyonlarında artış görüldü (P<0.05). Amigdalin+Dosetaksel verilen grupta ITGB1 ekspresyonundaki azalma anlamlıydı (P<0,001). Caspase-3 (P<0.05) ve Beclin-1 (P<0.05) immünoreaktivitelerinin her üç grupta kontrol grubuna kıyasla arttığı gözlendi.
SONUÇ: DU145 PK hücrelerinde Dosetaksel’in hücre ölümünü Amigdaline göre daha çok artırdığı, Amigdalin ve dosetakselin birlikte kullanıldığında ITGA2 ve ITGB1 ekspresyonlarını önemli şekilde azalttığı gözlemlenmiştir. Sonuçlarımız Amigdalin ve dosetakselin ikili tedavisinin prostat kanseri metastazlarının önüne geçebileceğini düşündürmektedir.

Keywords

Amigdalin, Dosetaksel, Prostat kanseri, İntegrin alfa2beta1.

Supporting Institution

Afyonkarahisar Health Science University Scientific Research Projects Coordination Unit

Project Number

19.TIP.013

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