Telomerase inhibitor MST-312 induces apoptosis of multiple myeloma cells and down-regulation of anti-apoptotic, proliferative and inflammatory genes.

Affiliation

Department of Hematology and Medical Laboratory Sciences, Faculty of Allied Medicine, Kerman University of Medical Sciences, Kerman, Iran. Electronic address: [Email]

Abstract

OBJECTIVE : The telomerase-based therapy of cancer has received a great deal of attention due to the fact that it is expressed in almost all of the cancer cells while it is inactivated in most of the normal somatic cells. Current investigation was aimed to examine the effects of namely telomerase inhibitor, the MST-312, as a chemically modified derivative of epigallocatechin gallate (EGCG), on human multiple myeloma cell line U-266.
METHODS : U-266 cells were cultured and then treated by MST-312. The viability of cultured cells was measured by both trypan blue staining and MTT assay techniques. To examine the apoptosis, annexin-V/7-AAD staining using flow cytometry method was employed. To analysis the expression of Bax, Bcl-2, c-Myc, hTERT, IL-6 and TNF-α genes, the quantitative real-time PCR was employed.
RESULTS : We observed the short-term dose-dependent cytotoxic and apoptotic effect of MST-312 against U-266 myeloma cells. Gene expression analysis indicated that the MST-312-based apoptosis was associated with up-regulation of pro-apoptotic gene (Bax) as well as down-regulation of anti-apoptotic (Bcl-2), proliferative (c-Myc, hTERT) and inflammatory (IL-6, TNF-α) genes.
CONCLUSIONS : These findings suggest that telomerase-based therapy using MST-312 may represent a novel promising strategy for treatment of multiple myeloma.

Keywords

Apoptosis,MST-312,Multiple myeloma,Telomerase,