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      • Time - and Concentration - Dependent Effects of Resveratrol on miR 15a and miR16-1 Expression and Apoptosis in the CCRF-CEM Acute Lymphoblastic Leukemia Cell Line

        Azimi, Ako,Hagh, Majid Farshdousti,Talebi, Mehdi,Yousefi, Bahman,feizi, Abbas Ali Hossein pour,Baradaran, Behzad,Movassaghpour, Ali Akbar,Shamsasenjan, Karim,Khanzedeh, Taghi,Ghaderi, Abdol Hasan,Heyd Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.15

        Background: Chemotherapy is one of the common approaches in treatment of cancers, especially leukemia. However, drug resistance phenomena reduce the likelihood of treatment success. Resveratrol is a herbal compound which through complicated processes makes some selected cells sensitive to treatment and induction of apoptosis. In the present study, the effects of resveratrol on the expression of miR 15a and miR16-1 and apoptosis in the CCRF-CEM cell line were investigated. Materials and Methods: The CCRF-CEM cell line was cultured under standard conditions and changes in miR 15a and miR 16-1 expression were analyzed by real time-PCR technique, with attention to reveratrol dose and time dependence. Also, apoptosis is evaluated by flow cytometry using annexin V and PI. Results: CCRF-CEM cells underwent dose-dependent apoptotic cell death in response to resveratrol. MiR 15a and miR 16-1 expression was up-regulated after 24 and 48 hours resveratrol treatment (p<0.05). Conclusions: The results of our study indicate that resveratrol induces apoptosis in a time and dose-dependent manner in CCRF-CEM cells. Also, increased expression level of miR 16-1 and miR 15a by means of resveratrol in CCRF-CEM cells might have a role in apoptosis induction and predisposition. According to our results resveratrol can be regarded as a dietary supplement to improve efficacy of anti-leukemia therapies.

      • KCI등재

        Investigation of BAX and BCL2 expression and apoptosis in a resveratrol- and prednisolone-treated human T-ALL cell line, CCRF-CEM

        Taghi Khanzadeh,Majid Farshdousti Hagh,Mehdi Talebi,Bahman Yousefi,Ako Azimi,Abbas Ali Hossein pour feizi,Behzad Baradaran 대한혈액학회 2018 Blood Research Vol.53 No.1

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

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        An investigation of methylation pattern changes in the IKZF1 promoter in patients with childhood B-cell acute lymphoblastic leukemia

        Mina Rahmani,Masoumeh Fardi,Majid Farshdousti Hagh,Abbas Ali Hosseinpour Feizi,Mehdi Talebi,Saeed Solali 대한혈액학회 2019 Blood Research Vol.54 No.2

        BackgroundIkaros family zinc finger 1 (IKZF1)is a transcription factor with an important role in control-ling hematopoietic proliferation and function, particularly lymphoid cell differentiation. It was previously shown that various mechanisms and expression patterns of Ikaros are linked to a variety of cancers. We hypothesized that aberrant methylation (hypomethylat-ion) of the IKZF1 promoter region might be one of the causes of B-cell acute lymphoblastic leukemia (B-ALL). In B-ALL patients, an increased expression of this gene is a potential cause of B-cell differentiation arrest and proliferation induction. Therefore, as more than 90% of patients with ALL are <15 years old, we investigated the methylation pattern of the IKZF1 promoter in childhood B-ALL.MethodsTwenty-five newly diagnosed B-ALL cases were included (all younger than 15 yr). In addi-tion, we selected 25 healthy age- and sex-matched children as the control group. We col-lected the blood samples in EDTA-containing tubes and isolated lymphocytes from whole blood using Ficoll 1.077 Lymphosep. Next, we extracted genomic DNA with the phe-nol/chloroform method. Two microgram of DNA per sample was treated with sodium bisulfite using the EpiTect Bisulfite Kit, followed by an assessment of DNA methylation by polymerase chain reaction (PCR) analysis of the bisulfite-modified genomic DNA.ResultsOur data highlighted a hypomethylated status of the IKZF1 promoter in the ALL cases (96% of the cases were unmethylated). In contrast, the control group samples were parti-ally methylated (68%).ConclusionThis study demonstrated a hypomethylated pattern of the IKZF1 promoter region in child-hood B-ALL, which might underlie the aberrant Ikaros expression patterns that were pre-viously linked to this malignancy.

      • KCI등재

        Investigating the expression pattern of the angiopoietin-Tie system in ALL and its correlation with baseline characteristics

        Saeed Zaka Khosravi,Samira Molaei Ramshe,Mehdi Allahbakhshian Farsani,Saeed Solali,Mohammadreza Moonesi,Majid Farshdousti Hagh 대한혈액학회 2021 Blood Research Vol.56 No.2

        Background Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children. Several environmental and genetic factors are known to be involved in its development and progression. The angiopoietin-Tie system is one of the most critical factors in angiogenesis, and its possible role in solid tumors and leukemia has been previously investigated. In this study, we examined the expression of these genes in ALL patients (early pre-B-ALL and pre-B-ALL) and compared them with normal samples. Methods Bone marrow samples were collected from 40 patients (aged 0‒19 yr) newly diagnosed with early pre-B-ALL or pre-B-ALL using molecular and flow cytometric tests and from 15 control individuals. For molecular tests, RNA extraction and cDNA synthesis were performed, and Ang1, Ang2, Ang4, Tie1, and Tie2 gene expression was examined by real-time polymerase chain reaction. Results Ang2, Tie1, and Tie2 gene expression were significantly increased in patients with ALL, whereas Ang1 gene expression was decreased. The Ang4 gene did not show significant expression changes between the two groups. Conclusion Changes in the expression of the Ang-Tie system indicate a possible role of angiogenesis in ALL prognosis. Moreover, such changes can be considered as potential diagnostic biomarkers or therapeutic targets.

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