Deoxypodophyllotoxin induces cytoprotective autophagy against apoptosis via inhibition of PI3K/AKT/mTOR pathway in osteosarcoma U2OS cells.
Pharmacol Rep
; 69(5): 878-884, 2017 Oct.
Article
in En
| MEDLINE
| ID: mdl-28623712
ABSTRACT
BACKGROUND:
A natural compound deoxypodophyllotoxin (DPT) possesses potent anti-proliferative and anti-tumor properties on several cancer types. It triggers cell cycle arrest followed by apoptosis through various cellular processes. However, it is limited to the action mechanism of DPT-mediated cell death modes via apoptosis and autophagy.METHODS:
Cell viability assay, morphological changes, annexin-V/propidium iodide (PI) assay, reactive oxygen species (ROS), acridine orange staining, and Western blot analyses were evaluated.RESULTS:
We demonstrated that DPT induced both apoptosis and autophagy via production of mitochondrial reactive oxygen species (ROS). DPT suppressed the PI3K/AKT/mTOR signaling cascades to lead autophagy process, resulting from conversion of light chain 3-I (LC3-I) into LC3-II and acidic vesicular organelles (AVOs) formation. Even if DPT-induced ROS were occurred in both apoptosis and autophagy, inhibition of ROS generation enhanced cell viability. Otherwise, 3-methyladeine (3-MA) impeding on autophagy accelerated an apoptotic response caused by DPT. Therefore, these findings suggest that DPT triggers cytoprotective autophagy against cytotoxic apoptosis.CONCLUSION:
Autophagy is required for cell survival by inhibition of apoptosis through down-regulation of PI3K/AKT/mTOR pathway against DPT-induced apoptosis in U2OS cells.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Podophyllotoxin
/
Osteosarcoma
/
Proto-Oncogene Proteins c-akt
/
TOR Serine-Threonine Kinases
/
Phosphoinositide-3 Kinase Inhibitors
/
Antineoplastic Agents, Phytogenic
Limits:
Humans
Language:
En
Journal:
Pharmacol Rep
Year:
2017
Document type:
Article