Resveratrol downregulates PI3K/Akt/mTOR signaling pathways in human U251 glioma cells.
Resveratrol (trans-3,4', 5-trihydroxystilbene) is a naturally occurring polyphenolic compound that has antiinflammatory, antioxidant, neuroprotective properties and acts as a chemopreventive agent. Resveratrol causes cell cycle arrest and induces apoptotic cell death in various types of cancer cells. In the current studies, the effect of resveratrol on phosphoinositide kinase-3 (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway was examined in human U251 glioma cells. Resveratrol decreased both the expression and phosphorylation of Akt. Inhibitors of PI3K (LY294002) and Akt (SH-6) enhanced resveratrol-induced LDH release and caspase-3 activation. Resveratrol reduced phosphorylation of ribosomal protein S6 and the mTOR inhibitor rapamycin further enhanced resveratrol-induced cell death. These results suggest that the downregulation of PI3K/Akt/mTOR signaling pathways may be an important mediator in resveratrol-induced apoptosis in glioma cells.
Jiang
Hao
H
Department of Neurology, Henry Ford Hospital, Detroit, Michigan 48202, USA. hjiang1@hfhs.org
Shang
Xia
X
Wu
Hongtao
H
Gautam
Subhash C
SC
Al-Holou
Shaza
S
Li
Christina
C
Kuo
Jarret
J
Zhang
Lijie
L
Chopp
Michael
M
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D019938:Cyclin D1 / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D005910:Glioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011494:Protein Kinases / Q000187:drug effects*; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors*; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*; D058570:TOR Serine-Threonine Kinases
D000972:Antineoplastic Agents, Phytogenic; C530104:CCND1 protein, human; D000081082:Phosphoinositide-3 Kinase Inhibitors; D013267:Stilbenes; D019938:Cyclin D1; D011494:Protein Kinases; C546842:MTOR protein, human; D051057:Proto-Oncogene Proteins c-akt; D058570:TOR Serine-Threonine Kinases; D053148:Caspase 3; D000077185:Resveratrol