Topoisomerase IIα content and topoisomerase II catalytic activity cannot explain drug sensitivities to topoisomerase II inhibitors in lung cancer cell lines

Kohichi Yamazaki, Hiroshi Isobe, Tarou Hanada, Tomoko Betsuyaku, Atsushi Hasegawa, Nobuyuki Hizawa, Shigeaki Ogura, Yoshikazu Kawakami

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

Purpose: Topoisomerase IIα content, topoisomerase II catalytic activity and drug sensitivities to the topoisomerase II inhibitors, doxorubicin and etoposide, were examined in a panel of 14 unselected human lung cancer cell lines in order to determine the relationship between topoisomerase II and drug sensitivities to the topoisomerase II inhibitors. Methods: Drug sensitivities were determined using a microculture tetrazolium assay. The topoisomerase IIα levels were determined by Western blot analysis and the topoisomerase II catalytic activity was determined using a decatenation assay of kinetoplast DNA, using nuclear protein from cells of each cell line. Results: Drug sensitivity tests revealed that small-cell lung cancer (SCLC) cell lines were more sensitive to drugs than non-small-cell lung cancer (NSCLC) cell lines. The relative topoisomerase IIα levels and relative topoisomerase II catalytic activity from SCLC cell lines (mean ± SD 0.89 ± 0.54 and 5.3 ± 3.4, respectively) were slightly higher than those from NSCLC cell lines (0.78 ± 0.56 and 4.0 ± 2.8, respectively), but the differences were not statistically significant, and not sufficient to account for the variation in drug sensitivities. Moreover, no clear association was observed between the topoisomerase IIα levels or the topoisomerase II catalytic activity and drug sensitivities in the cell lines studied. Conclusions: These findings suggest that the difference in drug sensitivities to doxorubicin and etoposide in human lung cancer cell lines might not be explainable by the topoisomerase IIα levels and topoisomerase II catalytic activity. Moreover, our results suggest that the topoisomerase IIα levels and topoisomerase II catalytic activity may play a minor role in the determination of clinical drug resistance of human lung cancers.

Original languageEnglish
Pages (from-to)192-198
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume39
Issue number3
DOIs
Publication statusPublished - 1997
Externally publishedYes

Fingerprint

Topoisomerase II Inhibitors
Type II DNA Topoisomerase
Catalyst activity
Lung Neoplasms
Cells
Cell Line
Pharmaceutical Preparations
Small Cell Lung Carcinoma
Etoposide
Non-Small Cell Lung Carcinoma
Doxorubicin
Assays
Kinetoplast DNA
Nuclear Proteins
Drug Resistance

Keywords

  • Drug sensitivity
  • Lung cancer
  • Topoisomerase II

ASJC Scopus subject areas

  • Cancer Research
  • Pharmacology
  • Oncology

Cite this

Topoisomerase IIα content and topoisomerase II catalytic activity cannot explain drug sensitivities to topoisomerase II inhibitors in lung cancer cell lines. / Yamazaki, Kohichi; Isobe, Hiroshi; Hanada, Tarou; Betsuyaku, Tomoko; Hasegawa, Atsushi; Hizawa, Nobuyuki; Ogura, Shigeaki; Kawakami, Yoshikazu.

In: Cancer Chemotherapy and Pharmacology, Vol. 39, No. 3, 1997, p. 192-198.

Research output: Contribution to journalArticle

Yamazaki, Kohichi ; Isobe, Hiroshi ; Hanada, Tarou ; Betsuyaku, Tomoko ; Hasegawa, Atsushi ; Hizawa, Nobuyuki ; Ogura, Shigeaki ; Kawakami, Yoshikazu. / Topoisomerase IIα content and topoisomerase II catalytic activity cannot explain drug sensitivities to topoisomerase II inhibitors in lung cancer cell lines. In: Cancer Chemotherapy and Pharmacology. 1997 ; Vol. 39, No. 3. pp. 192-198.
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abstract = "Purpose: Topoisomerase IIα content, topoisomerase II catalytic activity and drug sensitivities to the topoisomerase II inhibitors, doxorubicin and etoposide, were examined in a panel of 14 unselected human lung cancer cell lines in order to determine the relationship between topoisomerase II and drug sensitivities to the topoisomerase II inhibitors. Methods: Drug sensitivities were determined using a microculture tetrazolium assay. The topoisomerase IIα levels were determined by Western blot analysis and the topoisomerase II catalytic activity was determined using a decatenation assay of kinetoplast DNA, using nuclear protein from cells of each cell line. Results: Drug sensitivity tests revealed that small-cell lung cancer (SCLC) cell lines were more sensitive to drugs than non-small-cell lung cancer (NSCLC) cell lines. The relative topoisomerase IIα levels and relative topoisomerase II catalytic activity from SCLC cell lines (mean ± SD 0.89 ± 0.54 and 5.3 ± 3.4, respectively) were slightly higher than those from NSCLC cell lines (0.78 ± 0.56 and 4.0 ± 2.8, respectively), but the differences were not statistically significant, and not sufficient to account for the variation in drug sensitivities. Moreover, no clear association was observed between the topoisomerase IIα levels or the topoisomerase II catalytic activity and drug sensitivities in the cell lines studied. Conclusions: These findings suggest that the difference in drug sensitivities to doxorubicin and etoposide in human lung cancer cell lines might not be explainable by the topoisomerase IIα levels and topoisomerase II catalytic activity. Moreover, our results suggest that the topoisomerase IIα levels and topoisomerase II catalytic activity may play a minor role in the determination of clinical drug resistance of human lung cancers.",
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T1 - Topoisomerase IIα content and topoisomerase II catalytic activity cannot explain drug sensitivities to topoisomerase II inhibitors in lung cancer cell lines

AU - Yamazaki, Kohichi

AU - Isobe, Hiroshi

AU - Hanada, Tarou

AU - Betsuyaku, Tomoko

AU - Hasegawa, Atsushi

AU - Hizawa, Nobuyuki

AU - Ogura, Shigeaki

AU - Kawakami, Yoshikazu

PY - 1997

Y1 - 1997

N2 - Purpose: Topoisomerase IIα content, topoisomerase II catalytic activity and drug sensitivities to the topoisomerase II inhibitors, doxorubicin and etoposide, were examined in a panel of 14 unselected human lung cancer cell lines in order to determine the relationship between topoisomerase II and drug sensitivities to the topoisomerase II inhibitors. Methods: Drug sensitivities were determined using a microculture tetrazolium assay. The topoisomerase IIα levels were determined by Western blot analysis and the topoisomerase II catalytic activity was determined using a decatenation assay of kinetoplast DNA, using nuclear protein from cells of each cell line. Results: Drug sensitivity tests revealed that small-cell lung cancer (SCLC) cell lines were more sensitive to drugs than non-small-cell lung cancer (NSCLC) cell lines. The relative topoisomerase IIα levels and relative topoisomerase II catalytic activity from SCLC cell lines (mean ± SD 0.89 ± 0.54 and 5.3 ± 3.4, respectively) were slightly higher than those from NSCLC cell lines (0.78 ± 0.56 and 4.0 ± 2.8, respectively), but the differences were not statistically significant, and not sufficient to account for the variation in drug sensitivities. Moreover, no clear association was observed between the topoisomerase IIα levels or the topoisomerase II catalytic activity and drug sensitivities in the cell lines studied. Conclusions: These findings suggest that the difference in drug sensitivities to doxorubicin and etoposide in human lung cancer cell lines might not be explainable by the topoisomerase IIα levels and topoisomerase II catalytic activity. Moreover, our results suggest that the topoisomerase IIα levels and topoisomerase II catalytic activity may play a minor role in the determination of clinical drug resistance of human lung cancers.

AB - Purpose: Topoisomerase IIα content, topoisomerase II catalytic activity and drug sensitivities to the topoisomerase II inhibitors, doxorubicin and etoposide, were examined in a panel of 14 unselected human lung cancer cell lines in order to determine the relationship between topoisomerase II and drug sensitivities to the topoisomerase II inhibitors. Methods: Drug sensitivities were determined using a microculture tetrazolium assay. The topoisomerase IIα levels were determined by Western blot analysis and the topoisomerase II catalytic activity was determined using a decatenation assay of kinetoplast DNA, using nuclear protein from cells of each cell line. Results: Drug sensitivity tests revealed that small-cell lung cancer (SCLC) cell lines were more sensitive to drugs than non-small-cell lung cancer (NSCLC) cell lines. The relative topoisomerase IIα levels and relative topoisomerase II catalytic activity from SCLC cell lines (mean ± SD 0.89 ± 0.54 and 5.3 ± 3.4, respectively) were slightly higher than those from NSCLC cell lines (0.78 ± 0.56 and 4.0 ± 2.8, respectively), but the differences were not statistically significant, and not sufficient to account for the variation in drug sensitivities. Moreover, no clear association was observed between the topoisomerase IIα levels or the topoisomerase II catalytic activity and drug sensitivities in the cell lines studied. Conclusions: These findings suggest that the difference in drug sensitivities to doxorubicin and etoposide in human lung cancer cell lines might not be explainable by the topoisomerase IIα levels and topoisomerase II catalytic activity. Moreover, our results suggest that the topoisomerase IIα levels and topoisomerase II catalytic activity may play a minor role in the determination of clinical drug resistance of human lung cancers.

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KW - Lung cancer

KW - Topoisomerase II

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