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

• Published in: Journal of cellular biochemistry 2018-12, Vol.119 (12), p.10033-10040
• Main Authors: Zadi Heydarabad, Milad, Vatanmakanian, Mousa, Abdolalizadeh, Jalal, Mohammadi, Hamed, Azimi, Ako, Mousavi Ardehaie, Reza, Movasaghpour, Aliakbar, Farshdousti Hagh, Majid
• Format: Article
• Language: English
• Subjects: Acute lymphoblastic leukemia; Apoptosis; BAX gene; bcl-2-Associated X Protein - genetics; bcl-2-Associated X Protein - metabolism; Cell culture; Cell Line, Tumor; Chemotherapy; Deoxyribonucleic acid; DNA; DNA Methylation; Gene expression; Genes; Humans; Leukemia; Lymphatic leukemia; Lymphocytes T; methylation‐specific polymerase chain reaction; Polymerase chain reaction; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - physiopathology; Promoter Regions, Genetic; Proto-Oncogene Proteins c-bcl-2 - genetics; Proto-Oncogene Proteins c-bcl-2 - metabolism; Resveratrol; Resveratrol - pharmacology; Resveratrol - therapeutic use; Tumor cell lines
• ISSN: 0730-2312; 1097-4644
• DOI: 10.1002/jcb.27333

One of the fundamental barriers leading to failure of leukemia therapy is the resistance against conventional chemotherapies, common modality used to cure leukemia. Having the potential to trigger apoptosis in various human leukemia cell lines, resveratrol is regarded as a robust agent in chemotherapy regimens. The current study was aimed to assess whether the apoptotic effect of resveratrol on T‐cell acute lymphoblastic leukemia cell line, CCRF‐CEM, is exerted through DNA methylation of BAX and BCL2 gene promoters. For this purpose, the CCRF‐CEM cells were treated by resveratrol under standard cell culture. To analyze the promoter DNA methylation changes, we used methylation‐specific polymerase chain reaction technique following the resveratrol treatment at different dosages and time intervals. Based on our previous study, the resveratrol treatment can trigger apoptosis in CCRF‐CEM cell line via upregulation of apoptotic BAX gene and downregulation of antiapoptotic BCL2 gene. Despite these alterations in gene expression, the current study reveals no changes in DNA methylation patterns of subjected genes following the resveratrol treatment. Unchanged status of DNA methylation of BAX and BCL2 genes may suggest that resveratrol causes the gene expression changes through a distinct mechanism which requires further studies to be understood. Having a significant downregulation of BAX gene expression and upregulation of BCL2 gene expression following resveratrol treatment in various cancers, we were interested to study the possible relationship between expression and methylation status of promoter region in this gene after treatment by resveratrol in different doses and treatment intervals. To perform this, MSP method was used to show the methylation pattern changes in these cells.