European review for medical and pharmacological sciences | 2019
Preliminary results indicate resveratrol affects proliferation and apoptosis of leukemia cells by regulating PTEN/PI3K/AKT pathway.
Abstract
OBJECTIVE\nPTEN-PI3K/AKT signaling pathway is widely involved in the regulation of cell proliferation, cell cycle, apoptosis, and invasion. Resveratrol (Resv) is a natural botanical ingredient involved in several biological activities. It is still unclear in terms of whether Resv may exert anti-leukemia effects by regulating the PTEN-PI3K/AKT pathway. This study investigated the effect of Resv on leukemia cell proliferation and apoptosis by regulating PTEN-PI3K/AKT pathway.\n\n\nPATIENTS AND METHODS\nHuman normal peripheral blood PBMC cells, and human acute promyelocytic leukemia (APL) cell line NB-4 and HL-60 cells were cultured in vitro. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to detect Phosphatase and tensin homolog (PTEN) mRNA expression. Western blot was adopted to test PTEN protein expression. HL-60 and NB-4 cells were treated with 0, 5, 10, and 20 μM Resv, respectively. Cell proliferation was analyzed by cell counting kit8 (CCK-8) assay. The level of caspase-3 was measured by Western blot. HL-60 cells were divided into control group, 20 μM Resv treatment group, and Resv+PTEN inhibitor SF1670 group. Cell apoptosis was determined by flow cytometry. Cell proliferation was assessed by EdU staining.\n\n\nRESULTS\nCompared with peripheral blood mononuclear cell (PBMC), PTEN mRNA and protein levels were significantly decreased in NB-4 and HL-60 cells. Resv significantly inhibited the proliferation activity in HL-60 and NB-4 cells, and increased the activity of caspase-3. Resv treatment up-regulated the expression of PTEN and reduced the expression of p-AKT protein in HL-60 cells. However, Resv treatment markedly suppressed the proliferation of HL-60 and induced apoptosis. SF1670 treatment in the presence of Resv significantly antagonized the down-regulation of p-AKT protein expression induced by Resv, resulting in decreased apoptosis and enhanced cell proliferation.\n\n\nCONCLUSIONS\nResv can up-regulate PTEN expression and inhibit the activity of PI3K/AKT pathway to play an anti-leukemia effect through suppressing cell proliferation and inducing apoptosis.