Resveratrol-downregulated Phosphorylated Liver Kinase B1 Is Involved in Senescence of Acute Myeloid Leukemia Stem Cells

• Published in: Journal of Huazhong University of Science and Technology. Medical sciences Vol. 35; no. 4; pp. 485 - 489
• Main Authors: Peng, Dan-yue, Song, Hui, Liu, Ling-bo
• Format: Journal Article
• Language: English
• Published: Wuhan Huazhong University of Science and Technology 01.08.2015; Institute of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022,China
• Subjects: Apoptosis; Cell Line, Tumor; Cell Proliferation - drug effects; Cellular Senescence; Cyclin-Dependent Kinase Inhibitor p21 - genetics; Down-Regulation; Gene Expression Regulation, Neoplastic - drug effects; Humans; Leukemia, Myeloid, Acute - enzymology; Leukemia, Myeloid, Acute - genetics; Leukemia, Myeloid, Acute - pathology; Medicine; Medicine & Public Health; Neoplastic Stem Cells - drug effects; Phosphorylation; Protein-Serine-Threonine Kinases - genetics; Protein-Serine-Threonine Kinases - metabolism; Sirtuin 1 - genetics; Sirtuin 1 - metabolism; Stilbenes - pharmacology; β-半乳糖苷酶; 实时荧光PCR检测; 急性; 激酶; 白藜芦醇; 白血病; 磷酸化; 细胞衰老; phosphorylated liver kinase B1 (pLKB1); Sirtuin 1 (SIRT1); acute myeloid leukemia (AML); cellular senescence; leukemia stem cells (LSCs); resveratrol
• ISSN: 1672-0733; 1993-1352; 1993-1352
• DOI: 10.1007/s11596-015-1457-7

Summary： Senescence is an important obstacle to cancer development. Engaging a senescent response may be an effective way to cure acute myeloid leukemia （AML）. The aim of this study was to examine the effect of resveratrol-downregulated phosphorylated liver kinase B1 （pLKB1） on the senescence of acute myeloid leukemia （AML） stem cells. The protein expressions of pLKB 1 and Sirtuin 1 （SIRT1）, a regulator ofpLKB1, were measured in CD34＋CD38-KGla cells treated with resveratrol （40 μmol/L） or not by Western blotting. Senescence-related factors were examined, including p21 mRNA tested by real-time PCR, cell morphology by senescence-associated β-galactosidase （SA-β-gal） staining, cell pro- liferation by MTT assay and cell cycle by flow cytometry. Besides, apoptosis was flow cytometrically determined. The results showed that pLKB1 was highly expressed in CD34＋CD38- KGla cells, and resveratrol, which could downregulate pLKB1 through activation of SIRT1, induced senescence and apoptosis of CD34＋CD38- KGla cells. It was concluded that resveratrol-downregulated pLKB1 is in- volved in the senescence of AML stem cells.