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

Abstract

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.

• Authors: Hyung Joo Kim, Yeo Min Yoon, Jun Hee Lee, Sang Hun Lee
• Journal: Anticancer research (Anticancer Res) Vol. 39 Issue 10 Pg. 5515-5524 (Oct 2019) ISSN: 1791-7530 [Electronic] Greece
• PMID: 31570445 (Publication Type: Journal Article)
• Copyright: Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Antioxidants
• Endoplasmic Reticulum Chaperone BiP
• HSPA5 protein, human
• Heat-Shock Proteins
• Polysaccharides
• Protective Agents
• Reactive Oxygen Species
• fucoidan
• Protein Serine-Threonine Kinases
• eIF-2 Kinase
• Cisplatin

Topics

• Antioxidants (metabolism)
• Apoptosis (drug effects)
• Cell Cycle Checkpoints (drug effects)
• Cell Line
• Cisplatin (pharmacology)
• Endoplasmic Reticulum Chaperone BiP
• Endoplasmic Reticulum Stress (drug effects)
• Epithelial Cells (drug effects, metabolism)
• Heat-Shock Proteins (metabolism)
• Humans
• Kidney (drug effects, metabolism)
• Kidney Tubules, Proximal (drug effects, metabolism)
• Polysaccharides (pharmacology)
• Protective Agents (pharmacology)
• Protein Serine-Threonine Kinases (metabolism)
• Reactive Oxygen Species (metabolism)
• Th1 Cells (drug effects, metabolism)
• Up-Regulation (drug effects)
• eIF-2 Kinase (metabolism)