Inhibition of telomerase increases the susceptibility of human malignant glioblastoma cells to cisplatin-induced apoptosis

Yasuko Kondo, Seiji Kondo, Yoshikazu Tanaka, Talat Haqqi, Barbara P. Barna, John Kenneth Cowell

Research output: Contribution to journalArticle

160 Citations (Scopus)

Abstract

Malignant glioblastomas grow very rapidly and are generally resistant to either DNA-damaging drugs or γ-irradiation. If tumor cells could be made more susceptible to cell death with treatments, this would clearly represent a significant improvement in the success of treatment. Recently, telomerase has become a focus of interest among oncologists as a target for treating cancer cells. Telomerase elongates telomeric DNA repeats (TTAGGG)(n) and is important in protecting and replicating DNA. The vast majority of tumor cells, indeed, express telomerase activity whereas normal somatic cells, except for a few cells, do not. Since telomerase is essential for protecting DNA, we may be able to make tumors more sensitive to treatments with DNA-damaging drugs by inhibiting telomerase activity. In this study, we used cis-diamminedichloroplatinum (cisplatin)-sensitive U87-MG cells and cisplatin-resistant U251-MG of human malignant glioblastoma cell lines. U87-MG cells did not express telomerase activity, whereas telomerase was highly detected in U251-MG cells. Interestingly, inhibition of telomerase with an antisense telomerase expression vector not only decreased telomerase activity but also increased susceptibility to cisplatin-induced apoptotic cell death in U251-MG cells. These findings suggest that treatment with antisense telomerase may represent a new chemosensitisation for tumors resistant to anticancer drugs.

Original languageEnglish (US)
Pages (from-to)2243-2248
Number of pages6
JournalOncogene
Volume16
Issue number17
DOIs
StatePublished - Apr 30 1998
Externally publishedYes

Fingerprint

Telomerase
Glioblastoma
Cisplatin
Apoptosis
DNA
Neoplasms
Cell Death
Pharmaceutical Preparations
Therapeutics
Cell Line

Keywords

  • Apoptosis
  • Cisplatin
  • Glioma
  • Telomerase

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Inhibition of telomerase increases the susceptibility of human malignant glioblastoma cells to cisplatin-induced apoptosis. / Kondo, Yasuko; Kondo, Seiji; Tanaka, Yoshikazu; Haqqi, Talat; Barna, Barbara P.; Cowell, John Kenneth.

In: Oncogene, Vol. 16, No. 17, 30.04.1998, p. 2243-2248.

Research output: Contribution to journalArticle

Kondo, Yasuko ; Kondo, Seiji ; Tanaka, Yoshikazu ; Haqqi, Talat ; Barna, Barbara P. ; Cowell, John Kenneth. / Inhibition of telomerase increases the susceptibility of human malignant glioblastoma cells to cisplatin-induced apoptosis. In: Oncogene. 1998 ; Vol. 16, No. 17. pp. 2243-2248.
@article{6506c69582824917baeca32583350d06,
title = "Inhibition of telomerase increases the susceptibility of human malignant glioblastoma cells to cisplatin-induced apoptosis",
abstract = "Malignant glioblastomas grow very rapidly and are generally resistant to either DNA-damaging drugs or γ-irradiation. If tumor cells could be made more susceptible to cell death with treatments, this would clearly represent a significant improvement in the success of treatment. Recently, telomerase has become a focus of interest among oncologists as a target for treating cancer cells. Telomerase elongates telomeric DNA repeats (TTAGGG)(n) and is important in protecting and replicating DNA. The vast majority of tumor cells, indeed, express telomerase activity whereas normal somatic cells, except for a few cells, do not. Since telomerase is essential for protecting DNA, we may be able to make tumors more sensitive to treatments with DNA-damaging drugs by inhibiting telomerase activity. In this study, we used cis-diamminedichloroplatinum (cisplatin)-sensitive U87-MG cells and cisplatin-resistant U251-MG of human malignant glioblastoma cell lines. U87-MG cells did not express telomerase activity, whereas telomerase was highly detected in U251-MG cells. Interestingly, inhibition of telomerase with an antisense telomerase expression vector not only decreased telomerase activity but also increased susceptibility to cisplatin-induced apoptotic cell death in U251-MG cells. These findings suggest that treatment with antisense telomerase may represent a new chemosensitisation for tumors resistant to anticancer drugs.",
keywords = "Apoptosis, Cisplatin, Glioma, Telomerase",
author = "Yasuko Kondo and Seiji Kondo and Yoshikazu Tanaka and Talat Haqqi and Barna, {Barbara P.} and Cowell, {John Kenneth}",
year = "1998",
month = "4",
day = "30",
doi = "10.1038/sj.onc.1201754",
language = "English (US)",
volume = "16",
pages = "2243--2248",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "17",

}

TY - JOUR

T1 - Inhibition of telomerase increases the susceptibility of human malignant glioblastoma cells to cisplatin-induced apoptosis

AU - Kondo, Yasuko

AU - Kondo, Seiji

AU - Tanaka, Yoshikazu

AU - Haqqi, Talat

AU - Barna, Barbara P.

AU - Cowell, John Kenneth

PY - 1998/4/30

Y1 - 1998/4/30

N2 - Malignant glioblastomas grow very rapidly and are generally resistant to either DNA-damaging drugs or γ-irradiation. If tumor cells could be made more susceptible to cell death with treatments, this would clearly represent a significant improvement in the success of treatment. Recently, telomerase has become a focus of interest among oncologists as a target for treating cancer cells. Telomerase elongates telomeric DNA repeats (TTAGGG)(n) and is important in protecting and replicating DNA. The vast majority of tumor cells, indeed, express telomerase activity whereas normal somatic cells, except for a few cells, do not. Since telomerase is essential for protecting DNA, we may be able to make tumors more sensitive to treatments with DNA-damaging drugs by inhibiting telomerase activity. In this study, we used cis-diamminedichloroplatinum (cisplatin)-sensitive U87-MG cells and cisplatin-resistant U251-MG of human malignant glioblastoma cell lines. U87-MG cells did not express telomerase activity, whereas telomerase was highly detected in U251-MG cells. Interestingly, inhibition of telomerase with an antisense telomerase expression vector not only decreased telomerase activity but also increased susceptibility to cisplatin-induced apoptotic cell death in U251-MG cells. These findings suggest that treatment with antisense telomerase may represent a new chemosensitisation for tumors resistant to anticancer drugs.

AB - Malignant glioblastomas grow very rapidly and are generally resistant to either DNA-damaging drugs or γ-irradiation. If tumor cells could be made more susceptible to cell death with treatments, this would clearly represent a significant improvement in the success of treatment. Recently, telomerase has become a focus of interest among oncologists as a target for treating cancer cells. Telomerase elongates telomeric DNA repeats (TTAGGG)(n) and is important in protecting and replicating DNA. The vast majority of tumor cells, indeed, express telomerase activity whereas normal somatic cells, except for a few cells, do not. Since telomerase is essential for protecting DNA, we may be able to make tumors more sensitive to treatments with DNA-damaging drugs by inhibiting telomerase activity. In this study, we used cis-diamminedichloroplatinum (cisplatin)-sensitive U87-MG cells and cisplatin-resistant U251-MG of human malignant glioblastoma cell lines. U87-MG cells did not express telomerase activity, whereas telomerase was highly detected in U251-MG cells. Interestingly, inhibition of telomerase with an antisense telomerase expression vector not only decreased telomerase activity but also increased susceptibility to cisplatin-induced apoptotic cell death in U251-MG cells. These findings suggest that treatment with antisense telomerase may represent a new chemosensitisation for tumors resistant to anticancer drugs.

KW - Apoptosis

KW - Cisplatin

KW - Glioma

KW - Telomerase

UR - http://www.scopus.com/inward/record.url?scp=0032580369&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032580369&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1201754

DO - 10.1038/sj.onc.1201754

M3 - Article

VL - 16

SP - 2243

EP - 2248

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 17

ER -