Telomerase Inhibition and Cell Growth Arrest after Telomestatin Treatment in Multiple Myeloma

Masood A. Shammas, Robert J. Shmookler Reis, Cheng Li, Hemanta Koley, Laurence Hurley, Kenneth C. Anderson, Nikhil C. Munshi

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Abstract

Purpose: The aim of this study was to test the efficacy of telomestatin, an intramolecular G-quadruplex intercalating drug with specificity for telomeric sequences, as a potential therapeutic agent for multiple myeloma. Experimental Design: We treated ARD, ARP, and MM1S myeloma cells with various concentrations of telomestatin for 7 days and evaluated for telomerase activity. Myeloma cells were treated with the minimal effective telomestatin concentration for 3-5 weeks. Every 7th day the fraction of live cells was determined by trypan blue exclusion, aliquots of cells were removed for various molecular assays, and the remaining cells were replated at the same cell number and at the same concentration of telomestatin. Telomere length, apoptosis, and gene expression changes were monitored as described in detail in "Materials and Methods." Results: Telomestatin treatment led to inhibition of telomerase activity, reduction in telomere length, and apoptotic cell death in ARD, MMLS, and ARP myeloma cells. Gene expression profile after 1 and 7 days of telomestatin treatment revealed ≥2-fold change in only 6 (0.027%) and 51 (0.23%) of 33,000 genes surveyed, respectively. No changes were seen in expression of genes involved in cell cycle, apoptosis, DNA repair, or recombination. Conclusions: These results demonstrate that telomestatin exerts its antiproliferative and proapoptotic effects in myeloma cells via inhibition of telomerase and subsequent reduction in telomere length. We conclude that telomerase is an important potential therapeutic target for multiple myeloma therapy, and G-quadruplex interacting agents with specificity for binding to telomeric sequences can be important agents for additional evaluation.

Original languageEnglish (US)
Pages (from-to)770-776
Number of pages7
JournalClinical Cancer Research
Volume10
Issue number2
DOIs
StatePublished - Jan 15 2004

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Telomerase
Multiple Myeloma
Growth
Telomere
G-Quadruplexes
Apoptosis
Gene Expression
Trypan Blue
telomestatin
Transcriptome
DNA Repair
Genetic Recombination
Cell Cycle
Cell Death
Research Design
Therapeutics
Cell Count
Pharmaceutical Preparations
Genes

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Shammas, M. A., Shmookler Reis, R. J., Li, C., Koley, H., Hurley, L., Anderson, K. C., & Munshi, N. C. (2004). Telomerase Inhibition and Cell Growth Arrest after Telomestatin Treatment in Multiple Myeloma. Clinical Cancer Research, 10(2), 770-776. https://doi.org/10.1158/1078-0432.CCR-0793-03

Telomerase Inhibition and Cell Growth Arrest after Telomestatin Treatment in Multiple Myeloma. / Shammas, Masood A.; Shmookler Reis, Robert J.; Li, Cheng; Koley, Hemanta; Hurley, Laurence; Anderson, Kenneth C.; Munshi, Nikhil C.

In: Clinical Cancer Research, Vol. 10, No. 2, 15.01.2004, p. 770-776.

Research output: Contribution to journalArticle

Shammas, MA, Shmookler Reis, RJ, Li, C, Koley, H, Hurley, L, Anderson, KC & Munshi, NC 2004, 'Telomerase Inhibition and Cell Growth Arrest after Telomestatin Treatment in Multiple Myeloma', Clinical Cancer Research, vol. 10, no. 2, pp. 770-776. https://doi.org/10.1158/1078-0432.CCR-0793-03
Shammas, Masood A. ; Shmookler Reis, Robert J. ; Li, Cheng ; Koley, Hemanta ; Hurley, Laurence ; Anderson, Kenneth C. ; Munshi, Nikhil C. / Telomerase Inhibition and Cell Growth Arrest after Telomestatin Treatment in Multiple Myeloma. In: Clinical Cancer Research. 2004 ; Vol. 10, No. 2. pp. 770-776.
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