Protective Role of Fucoidan on Cisplatin-mediated ER Stress in Renal Proximal Tubule Epithelial Cells

Autor: Yeo Min Yoon, Sang Hun Lee, Jun Hee Lee, Hyung Joo Kim
Rok vydání: 2019
Předmět:
Zdroj: Anticancer Research. 39:5515-5524
ISSN: 1791-7530
0250-7005
DOI: 10.21873/anticanres.13744
Popis: Background/aim Administration of cisplatin in cancer patients is limited by the kidney-related adverse effects; however, a protective strategy is absent. We hypothesized that fucoidan protects the proximal tubule epithelial (TH-1) cells against the effects of cisplatin. Materials and methods To assess the effect of fucoidan, its effect on reactive oxygen species (ROS) formation, endoplasmic reticulum (ER) stress response, DNA damage response (DDR), apoptosis, and cell-cycle arrest in TH-1 cells was investigated. Results Cisplatin increased the accumulation of ROS, leading to excessive ER stress. In presence of cisplatin, treatment of TH-1 cells with fucoidan significantly reduced the ER stress by maintaining the complex of GRP78 with PERK and IRE1α. In particular, fucoidan enhanced the antioxidative capacity through up-regulation of PrPC Furthermore, fucoidan suppressed cisplatin-induced apoptosis and cell-cycle arrest, whereas silencing of PRNP blocked these effects of fucoidan. Conclusion Fucoidan may be a potential adjuvant therapy for cancer patients treated with cisplatin as it preserves renal functionality.
Databáze: OpenAIRE