Original article Evaluation of the miRNA profiling and effectiveness of the propolis on B-cell acute lymphoblastic leukemia cell line Ugur Cem Yilmaz a , Bakiye Goker Bagca b, *, Emin Karaca c , Asude Durmaz c , Burak Durmaz c , Ayca Aykut c , Husniye Kayalar d , Cigir Biray Avci b , Sunde Yilmaz Susluer b , Cumhur Gunduz b , Ozgur Cogulu c a Ege University, Faculty of Medicine, Izmir, Turkey b Ege University, Faculty of Medicine, Department of Medical Biology, Izmir, Turkey c Ege University, Faculty of Medicine, Department of Medical Genetics, Izmir, Turkey d Ege University, Faculty of Pharmacy, Izmir, Turkey A R T I C L E I N F O Article history: Received 5 October 2016 Received in revised form 17 October 2016 Accepted 17 October 2016 Keywords: Acute lymphoblastic leukemia miRNA Propolis Apoptosis A B S T R A C T Acute lymphoblastic leukemia (ALL) is one of the most frequent causes of death from cancer. Since the discovery of chemotherapeutic agents, ALL has become a model for improvement of survival. In parallel to this, serious side effects were observed and new natural therapeutic options has been discussed. One of these substances is called propolis which is a resinous substance gathered by honeybees. In the molecular era, miRNAs have been shown to play crucial roles in the development of many clinical conditions. The aim of this study is to evaluate the effect of Aydın propolis on 81 human miRNA activity in CCRF-SB leukemia cell line. Apoptotic effects of propolis on cell lines were also evaluated and apoptosis were found to be induced 1.5 fold in B-cell leukemia cells. The expression of 63 miRNAs (46 miRNAs were downregulated, 19 miRNAs were upregulated) in propolis treated leukemia cells have changed significantly (p < 0.05). In conclusion propolis has changed expression of miRNAs which have epigenetic effects on leukemic cells. It is thought that it can be a promising agent for ALL treatment for future studies. ã 2016 Elsevier Masson SAS. All rights reserved. 1. Introduction Leukemias account for 20–30% of childhood malignancies. Acute lymphoblastic leukemia (ALL) in leukemias is the most common malignant disease in childhood. With the advancements in chemotherapeutic agents used in the treatment of ALL, the treatment success for childhood ALL has reached to 75–80%. However, those drugs have serious side effects that decrease the quality of life, therefore many studies including natural products have been studied in the treatment of cancer to minimize the toxicity of anticancer drugs. Among these natural products propolis, one of the most popular substance used in alternative medicine, is widely studied. Propolis is a resinous wax-like substance collected by bees. It possesses antimicrobial, antiinflammatory, antioxidant and antitumoral effects besides its preventive effects in a number of diseases such as heart disease, diabetes mellitus and hepatotoxicity [7–10]. Antitumoral effects of propolis were first demonstrated in mature mice-bearing Ehrlich carcinoma, and in the following years antitumor effects and the possible mechanisms in cancer treatment have been investigated in different cancer types [11– 13]. Local administration of polyphenolic derivatives of propolis into the exact site of tumor cell inoculation caused a delay in tumor formation and an increase in survival [14]. Although a number of anticarcinogenic mechanisms of propolis have been described, the mechanism behind the antitumor effect is still obscure [15]. MicroRNAs (miRNAs) are short (generally 19–24 nucleotides) noncoding single-stranded RNA molecules that are involved in posttranscriptional regulation by targeting messenger RNAs. They are known to regulate several protein-coding genes both in plants and animals. Numerous miRNAs have been implicated in a variety of cellular processes including differentiation, apoptosis, cell proliferation, embryonic development, stem cell renewal, stress response and metabolism [3,4]. Their profound impact on the regulation of numerous cellular processes clearly suggests that any aberration in miRNA biogenesis pathway or its regulation * Corresponding author at: Ege University Medical Faculty, Department of Medical Biology, Bornova, 35100, Izmir, Turkey. E-mail address: bakiye.goker@ege.edu.tr (B.G. Bagca). http://dx.doi.org/10.1016/j.biopha.2016.10.056 0753-3322/ã 2016 Elsevier Masson SAS. All rights reserved. Biomedicine & Pharmacotherapy 84 (2016) 1266–1273 Available online at ScienceDirect www.sciencedirect.com