repository
Ivermectin kills cancer cells via catastrophic changes in the endoplasmic reticulum structure
- Alternative Title
- Hae In Lee
- Author(s)
- 이해인
- Alternative Author(s)
- Hae In Lee
- Advisor
- 최경숙
- Department
- 일반대학원 의생명과학과
- Publisher
- The Graduate School, Ajou University
- Publication Year
- 2019-08
- Language
- eng
- Alternative Abstract
- Ivermectin (IVM), an antiparasitic drug, is now considered a strong candidate for repurposing as an anticancer drug. IVM has been known to induce apoptosis or autophagy in several cancer cells, but the underlying mechanisms to explain its anticancer effects still remain unclear. In this study, we found that induces dramatic alterations of the endoplasmic reticulum (ER) structure, including reorganization, vacuolation, and subsequent permeabilization of the ER, prior to cancer cell death. In addition, IVM increases ER stress, and pretreatment with cycloheximide, a protein synthesis inhibitor, markedly blocked IVM-induced ER stress, vacuolation and permeabilization of the ER, and cell death, but not ER reorganization. Furthermore, IVM induces the activation of ERK and p38, imbalance of ions, including Ca2+ and Cl-, and inhibition of these signals effectively attenuated IVM-induced vacuolation and permeabilization of the ER and subsequent cell death. Taken together, these results suggest that IVM-induced catastrophic changes in the ER, including the vacuolation and permeabilization of the ER, critically contribute to the anti-cancer effect of IVM. ER stress, imbalance of Ca2+ and Cl-, and activation of MAPK play crucial roles in this process.
- Fulltext
- Appears in Collections:
- Graduate School of Ajou University > Department of Biomedical Sciences > 3. Theses(Master)
- Files in This Item:
- There are no files associated with this item.
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.
-
- License
- STATISTICS
- Total Visit :3,350,496
- Total Download :1,746
- Today View :4,657
