PTEN over-expression by resveratrol in acute lymphoblastic leukemia cells along with suppression of AKT/PKB and ERK1/2 in genotoxic stress.
The bioactive components of dietary phytochemicals are in the spotlight of research institutes, due to their significant antioxidant activities and health-promoting properties. Resveratrol is a polyphenol which is found abundantly in grapes and berries and has long been known as a chemo-preventive agent. The main purpose of this study was to provide a new mechanistic insight into the growth inhibition of acute lymphoblastic leukemia cells by resveratrol along with a DNA damage agent. It was found that the treatment of pre-B ALL cells by resveratrol in the presence or absence of doxorubicin resulted in decreased cell viability and a synergistic increase in cytotoxicity. Cell death was accompanied by a significant increase in phosphorylated p53 at serine 15 and accumulation of PTEN. In addition, resveratrol inhibited the over-expression of p-AKT and p-ERK1/2. These findings clearly demonstrated that resveratrol and doxorubicin synergistically increase the cytotoxicity of pre-B ALL cells via the hyper-activation of two important tumor suppressor proteins and two major signal transduction pathways.
Cellular and Molecular Nutrition Department, School of Nutritional Science and Dietetics, Tehran University of Medical Sciences, Tehran, Iran.
Arman
A
Ghorbani
Hamid
H
Zand
Mahmood
M
Jeddi-Tehrani
Fariba
F
Koohdani
Farzad
F
Shidfar
Seyed Ali
SA
Keshavarz
D004249:DNA Damage / Q000235:genetics*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics*; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy* / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000378:metabolism* / Q000627:therapeutic use*
D013267:Stilbenes; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D000077185:Resveratrol