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Cross-resistance to camptothecin analogues in a mitoxantrone-resistant human breast carcinoma cell line is not due to DNA topoisomerase I alterations.
Cancer Res. 1995 Sep 15; 55(18):4004-9.CR

Abstract

We have previously described a mitoxantrone-resistant human breast carcinoma cell line, MCF7/MX, in which resistance was associated with a defect in the energy-dependent accumulation of mitoxantrone in the absence of P-glycoprotein overexpression (M. Nakagawa et al., Cancer Res. 52: 6175-6181, 1992). We now report that this cell line is highly cross-resistant to the camptothecin analogues topotecan (180-fold), 9-aminocamptothecin (120-fold), CPT-11 (56-fold), and SN38 (101-fold), but is only mildly cross-resistant to the parent compound camptothecin (3.2-fold) and 10,11-methylenedioxy-camptothecin (2.9-fold). Topotecan accumulation was decreased in MCF7/MX cells compared to parental MCF7/WT cells, and there was a corresponding reduction in topotecan-mediated stimulation of the enzyme/DNA complex formation in MCF7/MX cells compared to MCF7/WT cells. No overexpression of the multidrug resistance-associated protein was detected compared to parental MCF7/WT cells. Furthermore, both sensitive MCF7/WT and mitoxantrone-resistant MCF7/MX cells contain equal amounts of DNA topoisomerase I protein, and DNA relaxation activities were equal in both cell lines and inhibited to the same extent by topotecan and camptothecin. Thus, these results suggest a novel mechanism of resistance to topoisomerase I inhibitors in cancer cells.

Authors+Show Affiliations

Medicine Branch, National Cancer Institute, Bethesda, Maryland 20892, USA.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

7664272

Citation

Yang, C J., et al. "Cross-resistance to Camptothecin Analogues in a Mitoxantrone-resistant Human Breast Carcinoma Cell Line Is Not Due to DNA Topoisomerase I Alterations." Cancer Research, vol. 55, no. 18, 1995, pp. 4004-9.
Yang CJ, Horton JK, Cowan KH, et al. Cross-resistance to camptothecin analogues in a mitoxantrone-resistant human breast carcinoma cell line is not due to DNA topoisomerase I alterations. Cancer Res. 1995;55(18):4004-9.
Yang, C. J., Horton, J. K., Cowan, K. H., & Schneider, E. (1995). Cross-resistance to camptothecin analogues in a mitoxantrone-resistant human breast carcinoma cell line is not due to DNA topoisomerase I alterations. Cancer Research, 55(18), 4004-9.
Yang CJ, et al. Cross-resistance to Camptothecin Analogues in a Mitoxantrone-resistant Human Breast Carcinoma Cell Line Is Not Due to DNA Topoisomerase I Alterations. Cancer Res. 1995 Sep 15;55(18):4004-9. PubMed PMID: 7664272.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Cross-resistance to camptothecin analogues in a mitoxantrone-resistant human breast carcinoma cell line is not due to DNA topoisomerase I alterations. AU - Yang,C J, AU - Horton,J K, AU - Cowan,K H, AU - Schneider,E, PY - 1995/9/15/pubmed PY - 1995/9/15/medline PY - 1995/9/15/entrez SP - 4004 EP - 9 JF - Cancer research JO - Cancer Res VL - 55 IS - 18 N2 - We have previously described a mitoxantrone-resistant human breast carcinoma cell line, MCF7/MX, in which resistance was associated with a defect in the energy-dependent accumulation of mitoxantrone in the absence of P-glycoprotein overexpression (M. Nakagawa et al., Cancer Res. 52: 6175-6181, 1992). We now report that this cell line is highly cross-resistant to the camptothecin analogues topotecan (180-fold), 9-aminocamptothecin (120-fold), CPT-11 (56-fold), and SN38 (101-fold), but is only mildly cross-resistant to the parent compound camptothecin (3.2-fold) and 10,11-methylenedioxy-camptothecin (2.9-fold). Topotecan accumulation was decreased in MCF7/MX cells compared to parental MCF7/WT cells, and there was a corresponding reduction in topotecan-mediated stimulation of the enzyme/DNA complex formation in MCF7/MX cells compared to MCF7/WT cells. No overexpression of the multidrug resistance-associated protein was detected compared to parental MCF7/WT cells. Furthermore, both sensitive MCF7/WT and mitoxantrone-resistant MCF7/MX cells contain equal amounts of DNA topoisomerase I protein, and DNA relaxation activities were equal in both cell lines and inhibited to the same extent by topotecan and camptothecin. Thus, these results suggest a novel mechanism of resistance to topoisomerase I inhibitors in cancer cells. SN - 0008-5472 UR - https://www.unboundmedicine.com/medline/citation/7664272/Cross_resistance_to_camptothecin_analogues_in_a_mitoxantrone_resistant_human_breast_carcinoma_cell_line_is_not_due_to_DNA_topoisomerase_I_alterations_ L2 - http://cancerres.aacrjournals.org/cgi/pmidlookup?view=long&pmid=7664272 DB - PRIME DP - Unbound Medicine ER -