The Effect of Telomerase Inhibition on the Expression of Inflammatory Cytokines Affecting the Pathogenesis of Multiple Myeloma Cell Line U266

• Main Authors: saeede ghiyasi, zahra ameri, Gholamhossein Hassanshahi, roohollah mirzaee, mohsen ehsan, noushin pouryazdanpanah, shima kazemzadeh, ahmad fatemi
• Format: Article
• Language: fas
• Published: Qom University of Medical Sciences 2018-06-01
• Series: Majallah-i Dānishgāh-i ̒Ulūm-i Pizishkī-i Qum
• Subjects: multiple myeloma; tumor necrosis factor-alpha; interleukin-6; mst-312.
• Online Access: http://journal.muq.ac.ir/browse.php?a_code=A-10-968-1&slc_lang=en&sid=1

Background and Objectives: Telomerase is an enzyme, which is overexpressed in 80-90% of cancers. Simultaneous activities of telomerase and NF-κB are required for progression of many cancers. In recent years, researchers have found out a close relationship between telomerase and the transcription factor NF-κB. Increased expression of telomerase is associated with significant increases in the expression level of NF-κB and endogenous genes, such as IL-6 and TNF-α. In recent years, several methods have been proposed to inhibit telomerase in cancer cells. Therefore, If it is possible to inhibit telomerase activity and consequently reduce the expression of inflammatory cytokines, the NF-κB signaling pathway, and the expression of target genes in the multiple myeloma disease. In this study, the effect of MST-312 (a derivative of green tea) with telomerase inhibition activity, was investigated on the treated U266 cell line and the expression of inflammatory cytokines.   Methods: In this experimental study, U266 cells, were treated with different dosed of MST-312 for 48 hours, and cellular apoptosis, was assessed by Annexin V Apoptosis Detection Kit. Then, to assess the expression of IL-6 and TNF-α genes, cells were treated with MST-312 (2μM for 48 hours) and the RNA of these cells, was extracted. In the following, real-time PCR method was used to investigate gene expression level.   Results: In this study, an increase in apoptosis and a decrease in the expression of IL-6 and TNF-α genes in U266 cells, was observed after 48 hours of exposure with 2μM MST-312. In addition, no cytotoxic effect was observed on normal blood mononuclear cells.   Conclusion: The results of the present study indicated that inhibition of telomerase activity by MST-312, can be considered as a novel treatment strategy for multiple myeloma.