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Reduced DNA topoisomerase II activity and drug-induced DNA cleavage activity in an adriamycin-resistant human small cell lung carcinoma cell line.
Cancer Res. 1990 Jan 15; 50(2):304-9.CR

Abstract

In a previous study we suggested that, in addition to the reduced Adriamycin accumulation, part of the resistance in an Adriamycin-resistant human small cell lung carcinoma cell line (GLC4/ADR) could be explained by supposing a changed Adriamycin-DNA-topoisomerase II (Topo II) interaction. The present study showed that the Mr 170,000 P-glycoprotein was not overexpressed in GLC4/ADR and that verapamil did not reverse the Adriamycin resistance. GLC4/ADR expressed cross-resistance to teniposide, etoposide, 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA), and mitoxantrone. Further investigations of the drug-Topo II interaction revealed that the decatenation activity of Topo II was two- to threefold reduced in both cellular and nuclear extracts from GLC4/ADR. Topo I activities appeared similar in extracts from GLC4/ADR and the parental sensitive cell line (GLC4). The slight increase in doubling time from 15 to 18 h, while the cell cycle distribution remained unchanged, could not account for the reduced Topo II activity in GLC4/ADR. Etoposide and m-AMSA-induced DNA cleavage was 5-fold reduced in cellular extracts from GLC4/ADR. Inhibition of the decatenation activity of Topo II in the presence of VP-16 and m-AMSA was increased twofold in the cellular extracts from GLC4/ADR. Therefore, these results suggest that resistance of GLC4/ADR to Adriamycin was in part due to the reduced drug-induced formation of the cleavage complex.

Authors+Show Affiliations

Department of Internal Medicine, University Hospital, groningen, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

1967222

Citation

de Jong, S, et al. "Reduced DNA Topoisomerase II Activity and Drug-induced DNA Cleavage Activity in an Adriamycin-resistant Human Small Cell Lung Carcinoma Cell Line." Cancer Research, vol. 50, no. 2, 1990, pp. 304-9.
de Jong S, Zijlstra JG, de Vries EG, et al. Reduced DNA topoisomerase II activity and drug-induced DNA cleavage activity in an adriamycin-resistant human small cell lung carcinoma cell line. Cancer Res. 1990;50(2):304-9.
de Jong, S., Zijlstra, J. G., de Vries, E. G., & Mulder, N. H. (1990). Reduced DNA topoisomerase II activity and drug-induced DNA cleavage activity in an adriamycin-resistant human small cell lung carcinoma cell line. Cancer Research, 50(2), 304-9.
de Jong S, et al. Reduced DNA Topoisomerase II Activity and Drug-induced DNA Cleavage Activity in an Adriamycin-resistant Human Small Cell Lung Carcinoma Cell Line. Cancer Res. 1990 Jan 15;50(2):304-9. PubMed PMID: 1967222.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Reduced DNA topoisomerase II activity and drug-induced DNA cleavage activity in an adriamycin-resistant human small cell lung carcinoma cell line. AU - de Jong,S, AU - Zijlstra,J G, AU - de Vries,E G, AU - Mulder,N H, PY - 1990/1/15/pubmed PY - 1990/1/15/medline PY - 1990/1/15/entrez SP - 304 EP - 9 JF - Cancer research JO - Cancer Res VL - 50 IS - 2 N2 - In a previous study we suggested that, in addition to the reduced Adriamycin accumulation, part of the resistance in an Adriamycin-resistant human small cell lung carcinoma cell line (GLC4/ADR) could be explained by supposing a changed Adriamycin-DNA-topoisomerase II (Topo II) interaction. The present study showed that the Mr 170,000 P-glycoprotein was not overexpressed in GLC4/ADR and that verapamil did not reverse the Adriamycin resistance. GLC4/ADR expressed cross-resistance to teniposide, etoposide, 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA), and mitoxantrone. Further investigations of the drug-Topo II interaction revealed that the decatenation activity of Topo II was two- to threefold reduced in both cellular and nuclear extracts from GLC4/ADR. Topo I activities appeared similar in extracts from GLC4/ADR and the parental sensitive cell line (GLC4). The slight increase in doubling time from 15 to 18 h, while the cell cycle distribution remained unchanged, could not account for the reduced Topo II activity in GLC4/ADR. Etoposide and m-AMSA-induced DNA cleavage was 5-fold reduced in cellular extracts from GLC4/ADR. Inhibition of the decatenation activity of Topo II in the presence of VP-16 and m-AMSA was increased twofold in the cellular extracts from GLC4/ADR. Therefore, these results suggest that resistance of GLC4/ADR to Adriamycin was in part due to the reduced drug-induced formation of the cleavage complex. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/1967222/Reduced_DNA_topoisomerase_II_activity_and_drug_induced_DNA_cleavage_activity_in_an_adriamycin_resistant_human_small_cell_lung_carcinoma_cell_line_ L2 - https://medlineplus.gov/lungcancer.html DB - PRIME DP - Unbound Medicine ER -