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 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.
['Kim|Hyung Joo|HJ|', 'Yoon|Yeo Min|YM|', 'Lee|Jun Hee|JH|', 'Lee|Sang Hun|SH|']
D000975:Antioxidants D017209:Apoptosis D059447:Cell Cycle Checkpoints D002460:Cell Line D002945:Cisplatin D000091342:Endoplasmic Reticulum Chaperone BiP D059865:Endoplasmic Reticulum Stress D004847:Epithelial Cells D006360:Heat-Shock Proteins D006801:Humans D007668:Kidney D007687:Kidney Tubules, Proximal D011134:Polysaccharides D020011:Protective Agents D017346:Protein Serine-Threonine Kinases D017382:Reactive Oxygen Species D018417:Th1 Cells D015854:Up-Regulation D019892:eIF-2 Kinase
Fucoidan ER stress cisplatin ROS DNA damage cellular prion protein