title: Resveratrol suppresses constitutive activation of AKT via generation of ROS and induces apoptosis in diffuse large B cell lymphoma cell lines.
abstract: BACKGROUND
  We have recently shown that deregulation PI3-kinase/AKT survival pathway plays an important role in pathogenesis of diffuse large B cell lymphoma (DLBCL). In an attempt to identify newer therapeutic agents, we investigated the role of Resveratrol (trans-3,4', 5-trihydroxystilbene), a naturally occurring polyphenolic compound on a panel of diffuse large B-cell lymphoma (DLBCL) cells in causing inhibition of cell viability and inducing apoptosis.
  
  
  RESULTS
  We investigated the action of Resveratrol on DLBCL cells and found that Resveratrol inhibited cell viability and induced apoptosis by inhibition of constitutively activated AKT and its downstream targets via generation of reactive oxygen species (ROS). Simultaneously, Resveratrol treatment of DLBCL cell lines also caused ROS dependent upregulation of DR5; and interestingly, co-treatment of DLBCL with sub-toxic doses of TRAIL and Resveratrol synergistically induced apoptosis via utilizing DR5, on the other hand, gene silencing of DR5 abolished this effect.
  
  
  CONCLUSIONS
  Altogether, these data suggest that Resveratrol acts as a suppressor of AKT/PKB pathway leading to apoptosis via generation of ROS and at the same time primes DLBCL cells via up-regulation of DR5 to TRAIL-mediated apoptosis. These data raise the possibility that Resveratrol may have a future therapeutic role in DLBCL and possibly other malignancies with constitutive activation of the AKT/PKB pathway.
authors.affiliation: Human Cancer Genomic Research, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia.
authors.forename: Azhar R
authors.initials: AR
authors.lastname: Hussain
authors.forename: Shahab
authors.initials: S
authors.lastname: Uddin
authors.forename: Rong
authors.initials: R
authors.lastname: Bu
authors.forename: Omar S
authors.initials: OS
authors.lastname: Khan
authors.forename: Saeeda O
authors.initials: SO
authors.lastname: Ahmed
authors.forename: Maqbool
authors.initials: M
authors.lastname: Ahmed
authors.forename: Khawla S
authors.initials: KS
authors.lastname: Al-Kuraya
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D016403:Lymphoma, Large B-Cell, Diffuse / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013267:Stilbenes / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D013267:Stilbenes; D045304:Cytochromes c; D051057:Proto-Oncogene Proteins c-akt; D000077185:Resveratrol