Investigation ofBAXandBCL2expression and apoptosis in a resveratrol- and prednisolone-treated human T-ALL cell line, CCRF-CEM

Abstract

BackgroundThe numerous side effects and chemo-resistance of conventional chemical drugs in the treatment of malignancies have led to consideration of the anti-cancer properties of natural products. In the present study, we aimed to explore the apoptotic effect of two natural components, resveratrol and prednisolone, on the T acute lymphoblastic leukemia (ALL) cell line, CCRF-CEM. Our findings suggested the incorporation of these natural agents into drug regimens to treat patients with ALL.MethodsIn this study, we investigated the effect of different doses of resveratrol (15, 50 and 100 µM) and prednisolone (700 µM) on BAX (apoptosis promoter) and BCL2 (apoptosis inhibitor) expressions following 24 and 48 hours of treatment on CCRF-CEM cells, using real-time PCR, and on apoptosis induction using flow cytometry.ResultsThe results showed a time- and dose-dependent increase in BAX expression and a decrease in BCL2 expression. Apoptosis was induced in CCRF-CEM cells treated with resveratrol and prednisolone for 24 and 48 hours. Combined resveratrol and prednisolone treatment showed synergistic effects on the overexpression of BAX and the downregulation of BCL2. The drug combination had a greater influence on apoptosis induction compared with either drug administered alone after 48 hours of treatment.ConclusionThe results of this study suggested that resveratrol exhibited a remarkable efficacy to improve the influence of glucocorticoids drugs, especially prednisolone, to induce apoptosis in the CCRF-CEM cell line.

Apoptotic effect of resveratrol on human T‐ALL cell line CCRF‐CEM is unlikely exerted through alteration of BAX and BCL2 promoter methylation

“…19 Our findings revealed that the nonviable cells (PI-positive and annexin-positive cells, as dead or in end-stage apoptosis cells) were 0.32%, 0.73%, 2.32%, and 10.39%, respectively, for control, R15, R50, and R100 µM treatment groups for 24 hours.…”

A Novel PDE4D Inhibitor BPN14770 Reverses Scopolamine-Induced Cognitive Deficits via cAMP/SIRT1/Akt/Bcl-2 Pathway

“…Furthermore, administration of sirtinol reversed effects the of BPN14770 on SIRT1 and pAkt expression. It is well known that Bcl-2 is a member of the Bcl-2 family located on the outskirts of the mitochondria that inhibits pro-apoptotic proteins ( Khanzadeh et al, 2018 ). Bcl-2-associated X protein (Bax) is a pro-apoptotic member of the Bcl-2 family that forms an oligomeric pore upon activation, enabling pro-apoptotic factors such as cytochrome c to migrate from the mitochondria to the cytoplasm ( Westphal et al, 2014 ).…”

Apoptosis Induced by Prednisolone Occurs without Altering the Promoter Methylation of BAX and BCL-2 Genes in Acute Lymphoblastic Leukemia Cells CCRF-CEM

“…Researches have shown that GC affects cell proliferation and cell survival, differentiation, and metabolism in many tissues. GC in the lymphoid system produces IG, progresses the cell cycle and induces apoptosis in immature lymphoblast (Ghasemi et al, 2018;Khanzadeh et al, 2018). Studies have also shown that GC regulates immune responses and is clinically used to treat lymphoid malignancies, including ALL (Bachmann et al, 2010;Pelt, 2010;Smith and Cidlowski, 2010;Papich, 2015;Azimi et al, 2016).…”

“…The appropriated dose of prednisolone (700 µM) added to CCRF-CEM cells. After 24 and 48 h, treated cells prepared for extraction of DNA and protein (Khanzadeh et al, 2018).…”