Selenoesters and Selenoanhydrides as Novel Agents Against Resistant Breast Cancer

Abstract

Background/aim: Selenium-containing compounds are becoming new alternatives in experimental chemotherapy in order to overcome multidrug resistance in cancer. The main goal of this study was to determine whether combined treatment with new Se-compounds would increase the effect of conventional doxorubicin chemotherapy in breast cancer cell lines.

Materials and methods: Se-compounds were evaluated regarding their cytotoxic and apoptosis-inducing effect on MCF-7 and ATP-binding cassette subfamily B member 1 (ABCB1)-overexpressing KCR breast cancer cell lines. Moreover, the interaction of Se-compounds with doxorubicin was assessed using the MTT assay.

Results: Selenoanhydride exerted a selective activity towards the doxorubicin-resistant KCR cell line overexpressing ABCB1. Among the selenoesters, only ketone-containing selenoesters exerted significant cytotoxic activity against MCF-7 and KCR cell lines and the Se-compounds acted synergistically with doxorubicin on the KCR cell line.

Conclusion: The importance of the COSeCH₂COCH₃ and COSeCH₂CO(CH₃)₃ moieties for the cytotoxic and adjuvant role of Se-compounds was highlighted.

Keywords: ABCB1 (P-glycoprotein); Selenoesters; apoptosis; breast cancer; doxorubicin.