Inhibition of telomerase activity as a measure of tumor cell killing by cisplatin in squamous cell carcinoma cell line

Hiroshi Mese, Yoshiya Ueyama, Atsushi Suzuki, Shuko Nakayama, Akira Sasaki, Hiroyuki Hamakawa, Tomohiro Matsumura

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Background: Telomerase is a ribonucleoprotein enzyme which is involved in the maintenance of chromosome ends. Telomerase activity is frequently associated with malignant phenotypes, and it can be considered a ubiquitous tumor marker. In this study we describe an approach for developing in vitro chemosensitivity assays based on the assessment of telomerase activity in squamous cell carcinoma to treatment with anticancer drugs. Methods: We used A431/CDDP1 and A431/CDDP2, two previously established cisplatin (CDDP)-resistant A431 sublines. These cell lines were not multidrug resistant but specifically resistant to the CDDP drug family. The telomeric repeat amplification protocol (TRAP assay) was used to measure telomerase activity in CDDP-resistant cell lines and to examine the effect of CDDP and other anticancer drugs on enzyme levels. We next analyzed the relations between telomerase activity and cytotoxic effects of CDDP in human squamous cell carcinoma (HSC2, HSC3, HSC4 and KB cell lines). Results: The telomerase activity of A431/CDDP1 and A431/CDDP2 was significantly higher than that of the parent A431 cell (A431/P) treated with CDDP and carboplatin at IC50. On the other hand, telomerase activity in these cell lines was not influenced by treatment with 5-fluorouracil, bleomycin, Adriamycin or taxol. The regression line derived from the quantitative analysis of the telomeric ladder versus IC50 of CDDP concentrations was analyzed. Telomerase activity was found to be positively correlated with the IC50 values for CDDP. Conclusions: The results of the present studies on in vitro squamous cell carcinoma cell lines indicate that telomerase activity inhibition can be used as a marker of tumor cell killing by CDDP. Therefore, the present investigation provides a rational basis for an in vitro chemosensitivity assay based on telomerase activity evaluation.

Original languageEnglish
Pages (from-to)136-142
Number of pages7
JournalChemotherapy
Volume47
Issue number2
DOIs
Publication statusPublished - 2001

Fingerprint

Telomerase
Cisplatin
Squamous Cell Carcinoma
Cell Line
Neoplasms
Inhibitory Concentration 50
Tumor Biomarkers
Pharmaceutical Preparations
KB Cells
Ribonucleoproteins
Carboplatin
Bleomycin
Enzymes
Paclitaxel
Fluorouracil
Doxorubicin
Chromosomes
Maintenance
Phenotype

Keywords

  • Chemosensitivity
  • Cisplatin
  • Squamous cell carcinoma
  • Telomerase activity

ASJC Scopus subject areas

  • Pharmacology (medical)

Cite this

Inhibition of telomerase activity as a measure of tumor cell killing by cisplatin in squamous cell carcinoma cell line. / Mese, Hiroshi; Ueyama, Yoshiya; Suzuki, Atsushi; Nakayama, Shuko; Sasaki, Akira; Hamakawa, Hiroyuki; Matsumura, Tomohiro.

In: Chemotherapy, Vol. 47, No. 2, 2001, p. 136-142.

Research output: Contribution to journalArticle

Mese, Hiroshi ; Ueyama, Yoshiya ; Suzuki, Atsushi ; Nakayama, Shuko ; Sasaki, Akira ; Hamakawa, Hiroyuki ; Matsumura, Tomohiro. / Inhibition of telomerase activity as a measure of tumor cell killing by cisplatin in squamous cell carcinoma cell line. In: Chemotherapy. 2001 ; Vol. 47, No. 2. pp. 136-142.
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AU - Sasaki, Akira

AU - Hamakawa, Hiroyuki

AU - Matsumura, Tomohiro

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AB - Background: Telomerase is a ribonucleoprotein enzyme which is involved in the maintenance of chromosome ends. Telomerase activity is frequently associated with malignant phenotypes, and it can be considered a ubiquitous tumor marker. In this study we describe an approach for developing in vitro chemosensitivity assays based on the assessment of telomerase activity in squamous cell carcinoma to treatment with anticancer drugs. Methods: We used A431/CDDP1 and A431/CDDP2, two previously established cisplatin (CDDP)-resistant A431 sublines. These cell lines were not multidrug resistant but specifically resistant to the CDDP drug family. The telomeric repeat amplification protocol (TRAP assay) was used to measure telomerase activity in CDDP-resistant cell lines and to examine the effect of CDDP and other anticancer drugs on enzyme levels. We next analyzed the relations between telomerase activity and cytotoxic effects of CDDP in human squamous cell carcinoma (HSC2, HSC3, HSC4 and KB cell lines). Results: The telomerase activity of A431/CDDP1 and A431/CDDP2 was significantly higher than that of the parent A431 cell (A431/P) treated with CDDP and carboplatin at IC50. On the other hand, telomerase activity in these cell lines was not influenced by treatment with 5-fluorouracil, bleomycin, Adriamycin or taxol. The regression line derived from the quantitative analysis of the telomeric ladder versus IC50 of CDDP concentrations was analyzed. Telomerase activity was found to be positively correlated with the IC50 values for CDDP. Conclusions: The results of the present studies on in vitro squamous cell carcinoma cell lines indicate that telomerase activity inhibition can be used as a marker of tumor cell killing by CDDP. Therefore, the present investigation provides a rational basis for an in vitro chemosensitivity assay based on telomerase activity evaluation.

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