Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

Buthionine sulphoximine-mediated sensitisation of etoposide-resistant human breast cancer MCF7 cells overexpressing the multidrug resistance-associated protein involves increased drug accumulation

Abstract

Preincubation of etoposide-resistant human MCF7 breast cancer cells (MCF7/VP) with buthionine sulphoximine (BSO) resulted in their sensitisation to etoposide and vincristine. Chemosensitisation was accompanied by elevated intracellular drug levels. In contrast, simultaneous exposure to BSO did not result in increased drug accumulation. Similar, but quantitatively smaller, effects were also observed when sensitive wild-type MCF7/WT cells were treated with BSO. In agreement with its effect on drug accumulation, BSO pretreatment also increased VP-16-stimulated cleavable complex formation between DNA topoisomerase II and cellular DNA. BSO treatment also led to a significant increase in acid-precipitable VP-16 levels in MCF7/VP, but not MCF7/WT cells. In contrast, no clear effects of BSO on drug efflux were observed and drug retention was only minimally increased after BSO treatment of both MCF7/WT and MCF7/VP cells and no difference between the two cell lines was detected. Thus, chemosensitisation by BSO appeared to be mediated through increased intracellular drug concentrations and/or protein binding.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schneider, E., Yamazaki, H., Sinha, B. et al. Buthionine sulphoximine-mediated sensitisation of etoposide-resistant human breast cancer MCF7 cells overexpressing the multidrug resistance-associated protein involves increased drug accumulation. Br J Cancer 71, 738–743 (1995). https://doi.org/10.1038/bjc.1995.144

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/bjc.1995.144

This article is cited by

Search

Quick links