Studying Effects of Auraptene on HTLV-1 Enfected Leukemia/Lymphoma Cells in Vitro

Auraptene, also known as 7-geranyloxycoumarin, is the most abundant prenyloxycoumarin identified in nature. This coumarin derivative is mainly synthesized by plants belonging to Rutaceae and Umbeliferae families. Auraptene possessed a wide range of pharmacological properties including antioxidantive, anti-inflammatory, antimicrobial, antigenotoxic and neuroprotective effects. Adult T-cell leukemia/lymphoma (ATLL) is a peripheral T-cell lymphoma caused by human T-cell leukemia/lymphoma virus type1 (HTLV-1). Iran, especially Khorasan province, is known as one of the endemic regions for HTLV-1. Despite advances in treatment of ATLL, the average survival rate of this malignancy is low. In present study, we investigated auraptene effects on the expression of CSC markers in human Adult T-cell leukemia/lymphoma cells. In this regard, MT-2 cells were treated with combination of 20 mg/ml auraptene and 2 mM arsenic for 72 h, while cells treated with 0.1% DMSO and 2 mM arsenic (used as auraptene solvent) were considered as relevant control. Then, the total cellular RNA was extracted and treated with DNase I. In the following, cDNAs were synthesized by M-MuLV reverse transcriptase, and their fidelity was confirmed by PCR using GAPDH primers. Real-time RT-PCR was conducted using SYBR green mix and specific primers for CD44 and BMI-1. Results of current study revealed that auraptene (in non-toxic concentration) significantly (p<0.05) down regulated the expression of CD44 and BMI-1 in MT-2 cells. Accordingly, this natural coumarin could be considered as an effective agent to attenuate malignant properties of human ATLL cells in future in vivo studies.

Keywords:

Auraptene , ATLL , HTLV-1 , CD44 , BMI-1