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Silencing of myeloid cell leukemia-1 by small interfering RNA improves chemosensitivity to etoposide in u-937 leukemic cells

Jafarlou M, Baradaran B, Shanehbandi D, Saedi TA, Jafarlou V, Karimi P, et al.

J Biol Regul Homeost Agents, 2016 Jan-Mar;30(1):55-65.
PMID: 27049076

A key issue in the treatment of acute myeloid leukemia (AML) is the development of drug resistance to chemotherapeutic agents. Overexpression of myeloid cell leukemia-1 (Mcl-1), an anti-apoptotic protein, is associated with tumor progression and drug resistance in leukemia and several cancers. The purpose of this study was to investigate the effect of specific Mcl-1 small interference RNA (siRNA) on the proliferation and chemosensitivity of U-937 AML cell to etoposide. The siRNA transfection was conducted using Lipofectamine 2000. Quantitative real-time RT-PCR (qRT-PCR) and Western blot analysis were employed to measure the expression levels of mRNA and protein, respectively. To evaluate tumor cell growth after siRNA transfection, Trypan blue exclusion assay was conducted. The cytotoxic effects of siRNA and etoposide were determined using MTT assay on their own and in combination. DNA-histone ELISA and annexin-V/FITC assays were performed to study the apoptosis. Mcl-1 siRNA transfection significantly blocked the expression of Mcl-1 mRNA and protein in a time-dependent manner, leading to a strong growth inhibition and enhanced apoptosis (P less than 0.05). Furthermore, pretreatment with Mcl-1 siRNA, synergistically enhanced the cytotoxic and apoptotic effects of etoposide (P less than 0.05). Our results demonstrated that Mcl-1 plays a fundamental role in the survival and resistance of U-937 cells to etoposide. Therefore, Mcl-1 can be considered an attractive target in gene therapy of AML patients and siRNA-mediated silencing of this gene may be a novel strategy in AML treatment.
siRNA-mediated inhibition of survivin gene enhances the anti-cancer effect of etoposide in U-937 acute myeloid leukemia cells

Jafarlou M, Baradaran B, Shanehbandi D, Saedi TA, Jafarlou V, Ismail P, et al.

Cell Mol Biol (Noisy-le-grand), 2016 May 30;62(6):44-9.
PMID: 27262801

Acute myeloid leukemia (AML) is one of the most frequent types of leukemia which mostly affects adult people. Resistance to therapeutic drugs is considered as a major clinical concern resulting in a weaker response to chemotherapy, disease relapse and decreased survival rate. Survivin, a member of Inhibitor of Apoptosis Proteins (IAPs), is associated with drug resistance and inhibition of apoptotic mechanisms in numerous hematological malignancies. In the present study, we examined the combined effect of etoposide and siRNA-mediated silencing of survivin on U-937 acute myeloid leukemia cells. The AML cells were transfected with survivin specific siRNA and gene knockdown was confirmed by quantitative real time PCR and western blotting. Subsequently, U-937 cells were assessed for response to etoposide treatment and apoptosis rate was measured with flowcytometery. The cytotoxic effects in siRNA-etoposide group were measured and compared to etoposide single therapy group. Survivin siRNA effectively knocked down the mRNA and protein levels of survivin, which led to lower cell proliferation and enhanced apoptosis. Furthermore, combined treatment of etoposide and survivin siRNA synergistically increased the cell toxic effects of etoposide and its ability to induce apoptosis.
An overview of the history, applications, advantages, disadvantages and prospects of gene therapy

Jafarlou M, Baradaran B, Saedi TA, Jafarlou V, Shanehbandi D, Maralani M, et al.

J Biol Regul Homeost Agents, 2016 Apr-Jun;30(2):315-21.
PMID: 27358116

Gene therapy has become a significant issue in science-related news. The principal concept of gene therapy is an experimental technique that uses genes to treat or prevent disease. Although gene therapy was originally conceived as a way to treat life-threatening disorders (inborn defects, cancers) refractory to conventional treatment, it is now considered for many nonlife-threatening conditions, such as those adversely impacting a patients quality of life. An extensive range of efficacious vectors, delivery techniques, and approaches for developing gene-based interventions for diseases have evolved in the last decade. The lack of suitable treatment has become a rational basis for extending the scope of gene therapy. The aim of this review is to investigate the general methods by which genes are transferred and to give an overview to clinical applications. Maximizing the potential benefits of gene therapy requires efficient and sustained therapeutic gene expression in target cells, low toxicity, and a high safety profile. Gene therapy has made substantial progress albeit much slower than was initially predicted. This review also describes the basic science associated with many gene therapy vectors and the present progress of gene therapy carried out for various surface disorders and diseases. The conclusion is that, with increased pathobiological understanding and biotechnological improvements, gene therapy will become a standard part of clinical practice.
Enhancement of chemosensitivity by simultaneously silencing of Mcl-1 and Survivin genes using small interfering RNA in human myelomonocytic leukaemia

Jafarlou M, Shanehbandi D, Dehghan P, Mansoori B, Othman F, Baradaran B

Artif Cells Nanomed Biotechnol, 2018 Dec;46(8):1792-1798.
PMID: 29113504 DOI: 10.1080/21691401.2017.1392969

Acute myeloid leukaemia (AML) is a genetically heterogeneous, severe and rapidly progressing disease triggered by blocking granulocyte or monocyte differentiation and maturation. Overexpression of myeloid cell leukaemia-1 (Mcl-1) and Survivin is associated with drug resistance, tumour progression and inhibition of apoptotic mechanisms in leukaemia and several cancers. In the present study, we examined the combined effect of etoposide and dual siRNA-mediated silencing of Mcl-1 and Survivin on U-937 AML cells. The AML cells were co-transfected with Mcl-1 and Survivin-specific siRNAs and genes silencing were confirmed by quantitative real-time PCR and Western blotting. Subsequently, MTT assay was used for the evaluation of cytotoxic effects by dual siRNA and etoposide on their own and in combination. For the studying of apoptosis, DNA-histone ELISA and annexin-V/FITC assays were performed. Co-transfection of Mcl-1 and Survivin siRNA significantly blocked their expression at the mRNA and protein levels, leading to the induction of apoptosis and strong inhibition of growth (p
Berberis vulgaris fruit crude extract as a novel anti-leukaemic agent

Saedi TA, Ghafourian S, Jafarlou M, Sabariah MN, Ismail P, Eusni RM, et al.

J Biol Regul Homeost Agents, 2015 Apr-Jun;29(2):395-9.
PMID: 26122228

Tumor protein p53 encoded by the TP53 gene in humans is known as a cancer biomarker in patients diagnosed with cancer, and it plays an essential role in apoptosis, genomic stability, and inhibition of angiogenesis. Cancer therapies with common chemotherapy methods are effective, as known, but have some side effects. Berberis vulgaris is traditionally administrated as a cancer drug. The current research aims to evaluate p53 as a biomarker in WEHI-3 cell line and to demonstrate the Berberis vulgaris fruit crude extract (BVFCE) as a new anticancer drug. For this purpose, we evaluated the effect of BVFCE in different concentrations against WEHI-3cell line in vitro and determined the quantitative level of p53 gene in the treated WEHI-3 cells. The results demonstrated that even at only 1 mg/ml concentration of Berberis vulgaris crude extract, there was a low level of p53 biomarker expression on WEHI-3 cells in comparison with doxorubicin. Therefore, the current study suggests BVFCE as a reliable anti-leukaemic drug and candidate for anticancer therapy. However, further investigation need be carried out to confirm its efficiency in vivo.
The role of probiotic supplementation in inflammatory biomarkers in adults: an umbrella meta-analysis of randomized controlled trials

Faghfouri AH, Afrakoti LGMP, Kavyani Z, Nogourani ZS, Musazadeh V, Jafarlou M, et al.

Inflammopharmacology, 2023 Oct;31(5):2253-2268.
PMID: 37698776 DOI: 10.1007/s10787-023-01332-8

OBJECTIVE: Despite the increasing evidence for probiotics' anti-inflammatory effects, the results of meta-analyses remain inconsistent. The present umbrella meta-analysis aimed to investigate the effects of probiotic supplementation on inflammatory biomarkers.
METHODS: We performed a wide-ranging systematic search in several databases, including PubMed, Web of Science, Scopus, EMBASE, and Google Scholar up to April 2023. The overall effect sizes were calculated using effect size (ES) values and their corresponding confidence intervals (CI).
RESULTS: Out of a total of 580 related articles, 39 studies were qualified for inclusion in the analysis. The results of the analysis revealed a significant reduction of C-reactive protein (CRP) (ES = -1.02; 95% CI: -1.23, -0.80, p