Protective role of fucoidan on cisplatin-mediated er stress in renal proximal tubule epithelial cells

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 PrP^C. 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.