Unfolded Protein Response is Involved in Trans-Platinum (II) Complex-Induced Apoptosis in Prostate Cancer Cells via ROS Accumulation
Yükleniyor...
Dosyalar
Tarih
2019
Dergi Başlığı
Dergi ISSN
Cilt Başlığı
Yayıncı
Bentham Science Publ Ltd
Erişim Hakkı
info:eu-repo/semantics/closedAccess
Özet
Background: Prostate cancer is one of the most common cancer types and it is the sixth leading cause of cancer-related death in men worldwide. Even though novel treatment modalities have been developed, it still a lifethreatening disease. Therefore novel compounds are needed to improve the overall survival. Methods: In our study, it was aimed to evaluate the anti-cancer activity of newly synthesized Platinum (II) [Pt(II)] complex on DU145, LNCaP and PC-3 prostate cancer cell lines. The cytotoxic activity of Pt(II) complex was tested by SRB and ATP cell viability assays. To detect the mode of cell death; fluorescent staining, flow cytometry and western blot analyses were performed. Results: The Pt(II) complex treatment resulted in a decrease in cell viability and increasing levels of apoptotic markers (pyknotic nuclei, annexin-V, caspase 3/7 activity) and a decrease in mitochondrial membrane potential in a dose dependent manner. Among cell types, tested PC-3 cells were found to be more sensitive to Pt(II) complex, demonstrating elevation of DNA damage in this cell line. In addition, Pt(II) complex induced Endoplasmic Reticulum (ER) stress by triggering ROS generation. More importantly, pre-treatment with NAC alleviated Pt(II) complex-mediated ER stress and cell death in PC-3. Conclusion: These findings suggest an upstream role of ROS production in Pt(II) complex-induced ER stressmediated apoptotic cell death. Considering the ROS-mediated apoptosis inducing the effect of Pt(II) complex, it warrants further evaluation as a novel metal-containing anticancer drug candidate.
Açıklama
ORAL, ARZU YILMAZTEPE/0000-0003-0463-6818; Karakas, Didem/0000-0002-3781-6834
Anahtar Kelimeler
Prostate Cancer, Cytotoxicity, Apoptosis, Oxidative Stress, Unfolded Protein Response, Platinum(Ii) Complex
Kaynak
Anti-Cancer Agents In Medicinal Chemistry
WoS Q Değeri
Q3
Scopus Q Değeri
Q3
Cilt
19
Sayı
9
Künye
Karakas, D., Cevatemre, B., Oral, A. Y., Yilmaz, V. T., & Ulukaya, E. (2019). Unfolded Protein Response is Involved in Trans-Platinum (II) Complex-Induced Apoptosis in Prostate Cancer Cells via ROS Accumulation. ANTI-CANCER AGENTS IN MEDICINAL CHEMISTRY, 19(9), 1184–1195. https://doi.org/10.2174/1871520619666190409103334
