Effects of telomerase inhibitor on epigenetic chromatin modification enzymes in malignancies


Biray A. , DOGAN F., OZATES A. N. , Goker B., ABBASZADEH Z., Gunduz C.

JOURNAL OF CELLULAR BIOCHEMISTRY, vol.119, no.12, pp.9817-9824, 2018 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 119 Issue: 12
  • Publication Date: 2018
  • Doi Number: 10.1002/jcb.27301
  • Title of Journal : JOURNAL OF CELLULAR BIOCHEMISTRY
  • Page Numbers: pp.9817-9824
  • Keywords: BIBR1532, chronic myeloid leukemia, glioma, TUMOR-SUPPRESSOR FUNCTION, CHRONIC MYELOID-LEUKEMIA, TARGETING TELOMERASE, METHYLTRANSFERASE 1, CELL-PROLIFERATION, BREAST-CANCER, BIBR1532, METHYLATION, PROTEIN, LINES

Abstract

Telomerase has a critical role in cell proliferation, tumor maintaining, and therapy resistance, which act by modifying many signaling pathways. 2-[(E)-3-Naphtalen-2-yl-but-2-enoylamino]-benzoic acid (BIBR1532) is one of the most studied telomerase inhibitors, and it targets telomerase components TERC and TERT. In this novel study, we aimed to investigate the epigenetic effects of BIBR1532 on both hematologic malignancies and solid tumors. K-562 human chronic myeloid leukemia cell line and U87MG glioblastoma cell line were compared with control groups without BIBR1532 treatment. Cytotoxic effects of BIBR1532 were determined by using WST-1 assay. Apoptotic effects of BIBR1532 were detected by using annexin V method. To assess expression changes in the human epigenetic chromatin modification enzyme genes, total RNA was isolated from K-562 and U87MG cells treated with BIBR1532 and untreated control cells. BIBR1532 induced 2.41-fold apoptotic cell death in U87MG cell lines compared with control groups. Apoptosis was slightly induced in K-562 cells with BIBR1532 treatment compared with control cells. We observed that BIBR1532 also regulates similar genes in both cell lines, and it is useful on epigenetic mechanisms. As a result, telomerase inhibitor BIBR1532 has a significant effect on both hematological malignancies and solid tumors.