Investigation of telomerase inhibition effect on apoptosis of myeloma cell line U266

Abstract:
Background And Objectives
Telomerase-targeted therapy for cancer has received great attention because telomerase is expressed in almost all cancer cells but is inactive in most normal somatic cells. This study aimed to investigate the effects of telomerase inhibitor MST-312, a chemically modified derivative of epigallocatechin gallate (EGCG), on apoptosis of myeloma cell line U266.
Materials And Methods
In an Experimental study, U266 cells were treated with different concentrations of MST-312 at different times; then, cell viability by trypan blue exclusion assay, cell metabolic activity by MTT assay, and cell apoptosis by Annexin V Apoptosis Detection Kit were measured. To further investigate apoptosis, BAX and BCL2 gene expression of the treated cells was investigated by the quantitative Real-Time PCR.
Results
MST-312 exerted a dose-dependent short-term cytotoxic effect on myeloma cells. Over 50% decrease in the viability of treated cells was seen in 8 μM concentration of MST-312 within 48 h. The cytotoxic effect of MST-312 was concentration-dependent, with approximately 25, 46, and 62% reduction in metabolic activity after 48 h exposure to 2, 4, and 8 μM of MST-312, respectively. Gene expression analysis showed downregulation of antiapoptotic gene Bcl-2 and upregulation of apoptopic gene BAX.
Conclusions
Inhibition of telomerase activity by MST-312 represents a novel treatment strategy for Multiple Myeloma cancer.
Language:
Persian
Published:
Scientific Journal of Iranian Blood Transfusion Organization, Volume:14 Issue: 3, 2017
Pages:
204 to 217
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