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Pterostilbene induces cell apoptosis and inhibits lipogenesis in SKOV3 ovarian cancer cells by activation of AMPK-induced inhibition of Akt/mTOR signaling cascade

引用

BIOCELL 2021年第1期45卷 89-101页

作者： ATTALLA EL-KOTT EMAN ELBEALY FAHMY ELSAID HAITHAM EL-MEKKAWY ABD-EL-KARIM ABD-LATEIF abdulali taweel HEBA KHALIFA AHMAD KANDEEL KAREEM MORSY ESSAM IBRAHIM MASHAEL MOHAMMED BIN-MEFERIJ Biology Department College of ScienceKing Khalid UniversityAbha61413Saudi Arabia Zoology Department College of ScienceDamanhour UniversityDamanhour22511Egypt Biology Department College of Science for GirlsKing Khalid UniversityAbha61413Saudi Arabia Zoology Department College of ScienceMansoura UniversityMansoura35511Egypt Zoology Department College of ScienceFayoum UniversityFayoum63511Egypt Zoology Department Faculty of ScienceAl-Zawia UniversityAl-ZawiaLibya Biology Department Faculty of ScienceCairo UniversityCairo12611Egypt Research Center for Advanced Materials Science(RCAMS) King Khalid UniversityAbha61413Saudi Arabia Blood Products Quality Control and Research Department National Organization for Research and Control of BiologicalsCairo12611Egypt Biology Department College of SciencePrincess Nourah bint Abdulrahman UniversityRiyadhSaudi Arabia

This study investigates if the anti-tumor effect of Pterostilbene in the SKOV3 ovarian cancer(OC)cell line involves inhibition of cell metabolism and tested in this effect involves modulating AMPK and Akt-induced regulation of ***,SKOV3 cells were cultured in the humidified conditions in DMEM media for 24 h with or without increasing concentration of ***,the cells were incubated with Pterostilbene(IC_(50)=50μM)under similar conditions with or without pre-incubation with Dorsomorphin,an AMPK *** a dose-dependent manner,Pterostilbene inhibited SKOV3 cell survival and increased their lysate levels of lactate dehydrogenase(LDH)and single-stranded DNA(ssDNA).When SKOV3 cells were treated with 50μM Pterostilbene,Pterostilbene significantly suppressed cell migration and invasion,reduced lysate levels of lactic acid and the optical density of Oil Red O staining,and increased lysate glucose *** also increased levels of malondialdehyde(MDA),reactive oxygen species(ROS),and induced intrinsic cell apoptosis by upregulating protein levels of Bax and cleaved caspase-3 and reducing protein levels of ***,Pterostilbene reduced mRNA levels of sterol regulatory element-binding protein 1(SREBP-1),fatty acid synthase(FAS),acetyl CoA carboxylase-1(ACC-1),and AMP-activated protein kinase(AMPK).Furthermore,Pterostilbene increased the protein levels of p-AMPK,p-p53,p-raptor,p-TSC-2,but significantly decreased protein levels of p-Akt,p-TSC-2,p-mTOR,p-S6K1,and *** with Dorsomorphin(CC)abolished all the anti-tumorigenesis effects afforded by Pterostilbene and prevented Pterostilbene-induced phosphorylation of Akt,p53,and *** conclusion,the tumorsuppressive effect of Pterostilbene in SKOV3 cells involves the induction of ROS and inhibition of dysregulation cell metabolism mainly due to AMPK-induced Akt-dependent or independent suppression of mTOR.

关键词： Pterostilbene Ovarian cancer Lipogenesis Apoptosis AMPK

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