Journal
CANCER LETTERS
Volume 366, Issue 1, Pages 19-31Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2015.05.032
Keywords
Icariside II; Mitochondria; Lysosomes; Autophagosome; Hepatoblastoma
Categories
Funding
- National Natural Science Foundation of China [81202901]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Program for Changjiang Scholars and Innovative Research Team in University [PCSIRT-IRT1193]
Ask authors/readers for more resources
In this study, the anti-cancer effect of Icariside II (IS), a natural plant flavonoid, against hepatoblastoma cells and the underlying mechanisms were investigated. The in vitro and in vivo studies show that IS decreased the viability of human hepatoblastoma HepG2 cells in a concentration- and time-dependent manner and inhibited tumor growth in mice transplanted with H22 liver carcinomas. IS impaired mitochondria and lysosomes as evidenced by signs of induced mitochondrial and lysosomal membrane permeabilization, resulting in caspase activation and apoptosis. SQSTM1 up-regulation and autophagic flux measurements demonstrated that IS exposure also impaired autophagosome degradation which resulted in autophagosome accumulation, which plays a pro-survival role as the genetic knockdown of LOB further sensitized the IS-treated cells. Electron microscopy images showed that autophagosome engulfs ISimpaired mitochondria and lysosomes, thus blocking cytotoxicity induced by further leakage of the hydrolases from lysosomes and pro-apoptosis members from mitochondria. In conclusion, these data suggest that IS plays multiple roles as a promising chemotherapeutic agent that induces cell apoptosis involving both mitochondrial and lysosomal damage. (C) 2015 Elsevier Ireland Ltd. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available