An Organofluorine Isoselenocyanate Analogue of Sulforaphane Affects Antimetabolite 5-Fluorouracil’s Anticancer Activity: A Perspective for New Combinatory Therapy in Triple-Negative Breast Cancer
Małgorzata Milczarek,
Tomasz Cierpiał,
Piotr Kiełbasiński,
Milena Małecka-Giełdowska,
Marta Świtalska,
Joanna Wietrzyk,
Maciej Mazur,
Katarzyna Wiktorska
Affiliations
Małgorzata Milczarek
Laboratory of Translation Research, Department of Biomedical Research, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland
Tomasz Cierpiał
Division of Organic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland
Piotr Kiełbasiński
Division of Organic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, Poland
Milena Małecka-Giełdowska
Department of Laboratory Medicine, Medical University of Warsaw, Stefana Banacha 1A, 02-097 Warsaw, Poland
Marta Świtalska
Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, Poland
Joanna Wietrzyk
Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, Poland
Maciej Mazur
Faculty of Chemistry, University of Warsaw, Ludwika Pasteura 1, 02-093 Warsaw, Poland
Katarzyna Wiktorska
Laboratory of Translation Research, Department of Biomedical Research, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland
Antimetabolites, especially 5-fluorouracil, are commonly used clinically to treat breast, colon, and other cancers. However, their side effects and inefficiency in monotherapy have prompted further searches for new combinations. Thus, the anticancer effect of 5-fluorouracil (5-FU) and the sulforaphane analogue, 4-isoselenocyanato-1-butyl 4′-fluorobenzyl sulfoxide (ISC), were tested in in vitro and in vivo models of triple-negative breast cancer (TNBC) as a new option for this treatment-resistant and aggressive type of breast cancer. A synergic interaction between 5-FU and ISC was observed in the TNBC in vitro model MDA-MB-231 cell line, which led to enhanced antiproliferative effects. The results of in vitro studies were confirmed by in vivo tests, which demonstrated stronger tumor growth inhibition and additive interactions between 5-FU and ISC in the murine TNBC model. Moreover, the results of the body mass and blood analysis showed the safety of the tested combination. The mechanistic study revealed that the combined treatment triggered apoptosis and necrosis, as well as inhibited cell migration.
