Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UNIPROT:P42345 (
mTOR
)
26,049
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Glioblastoma (GBM) is the most common and aggressive primary brain tumor with great invasiveness and resistance to chemotherapy, which presents a treatment challenge. In this study, we investigated the antitumor effect of
Cedrol
, a sesquiterpene alcohol isolated from Cedrus atlantica, against GBM cells in vitro and in vivo.
Cedrol
was found to potently inhibit cell growth and induce intracellular ROS generation and DNA damage response. In addition,
Cedrol
induced significant G
0
/G
1
cell cycle arrest and cell apoptosis via the extrinsic (Fas/FasL/Caspase-8) and intrinsic (Bax/Bcl-2/Caspase-9) pathways. In addition,
Cedrol
had a synergistic effect with temozolomide (TMZ) and reduced drug resistance by blockage of the AKT/
mTOR
pathway.
Cedrol
suppressed tumor growth in both orthotopic and xenograft GBM animal models with low or no short-term acute toxicity or long-term accumulative toxicity. In a molecular docking study,
Cedrol
targeted the androgen receptor (AR), and reduced DHT-mediated AR nuclear translocation, downstream gene KLK3/TMPRSS2 expression and cell proliferation. Our study demonstrates that
Cedrol
may be a potential candidate for drug development for single or combination treatment with TMZ in GBM therapy.
...
PMID:Cedrol suppresses glioblastoma progression by triggering DNA damage and blocking nuclear translocation of the androgen receptor. 3298 40
