An Organofluorine Isoselenocyanate Analogue of Sulforaphane Affects Antimetabolite 5-Fluorouracil’s Anticancer Activity: A Perspective for New Combinatory Therapy in Triple-Negative Breast Cancer
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 sulforapha...
| Main Authors: | , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-08-01
|
| Series: | Molecules |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1420-3049/28/15/5808 |
| _version_ | 1797586247098564608 |
|---|---|
| author | Małgorzata Milczarek Tomasz Cierpiał Piotr Kiełbasiński Milena Małecka-Giełdowska Marta Świtalska Joanna Wietrzyk Maciej Mazur Katarzyna Wiktorska |
| author_facet | Małgorzata Milczarek Tomasz Cierpiał Piotr Kiełbasiński Milena Małecka-Giełdowska Marta Świtalska Joanna Wietrzyk Maciej Mazur Katarzyna Wiktorska |
| author_sort | Małgorzata Milczarek |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-11T00:20:39Z |
| format | Article |
| id | doaj.art-893d4dbcd99a4db0a763806046b6d9ed |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T00:20:39Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-893d4dbcd99a4db0a763806046b6d9ed2023-11-18T23:19:13ZengMDPI AGMolecules1420-30492023-08-012815580810.3390/molecules28155808An Organofluorine Isoselenocyanate Analogue of Sulforaphane Affects Antimetabolite 5-Fluorouracil’s Anticancer Activity: A Perspective for New Combinatory Therapy in Triple-Negative Breast CancerMałgorzata Milczarek0Tomasz Cierpiał1Piotr Kiełbasiński2Milena Małecka-Giełdowska3Marta Świtalska4Joanna Wietrzyk5Maciej Mazur6Katarzyna Wiktorska7Laboratory of Translation Research, Department of Biomedical Research, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, PolandDivision of Organic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, PolandDivision of Organic Chemistry, Centre of Molecular and Macromolecular Studies, Polish Academy of Sciences, Sienkiewicza 112, 90-363 Łódź, PolandDepartment of Laboratory Medicine, Medical University of Warsaw, Stefana Banacha 1A, 02-097 Warsaw, PolandHirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, PolandHirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Rudolfa Weigla 12, 53-114 Wrocław, PolandFaculty of Chemistry, University of Warsaw, Ludwika Pasteura 1, 02-093 Warsaw, PolandLaboratory of Translation Research, Department of Biomedical Research, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, PolandAntimetabolites, 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.https://www.mdpi.com/1420-3049/28/15/5808antimetabolitesisoselenocyanate5-fluorouracilsulforaphaneanticancer effect |
| spellingShingle | Małgorzata Milczarek Tomasz Cierpiał Piotr Kiełbasiński Milena Małecka-Giełdowska Marta Świtalska Joanna Wietrzyk Maciej Mazur Katarzyna Wiktorska An Organofluorine Isoselenocyanate Analogue of Sulforaphane Affects Antimetabolite 5-Fluorouracil’s Anticancer Activity: A Perspective for New Combinatory Therapy in Triple-Negative Breast Cancer Molecules antimetabolites isoselenocyanate 5-fluorouracil sulforaphane anticancer effect |
| title | An Organofluorine Isoselenocyanate Analogue of Sulforaphane Affects Antimetabolite 5-Fluorouracil’s Anticancer Activity: A Perspective for New Combinatory Therapy in Triple-Negative Breast Cancer |
| title_full | An Organofluorine Isoselenocyanate Analogue of Sulforaphane Affects Antimetabolite 5-Fluorouracil’s Anticancer Activity: A Perspective for New Combinatory Therapy in Triple-Negative Breast Cancer |
| title_fullStr | An Organofluorine Isoselenocyanate Analogue of Sulforaphane Affects Antimetabolite 5-Fluorouracil’s Anticancer Activity: A Perspective for New Combinatory Therapy in Triple-Negative Breast Cancer |
| title_full_unstemmed | An Organofluorine Isoselenocyanate Analogue of Sulforaphane Affects Antimetabolite 5-Fluorouracil’s Anticancer Activity: A Perspective for New Combinatory Therapy in Triple-Negative Breast Cancer |
| title_short | An Organofluorine Isoselenocyanate Analogue of Sulforaphane Affects Antimetabolite 5-Fluorouracil’s Anticancer Activity: A Perspective for New Combinatory Therapy in Triple-Negative Breast Cancer |
| title_sort | organofluorine isoselenocyanate analogue of sulforaphane affects antimetabolite 5 fluorouracil s anticancer activity a perspective for new combinatory therapy in triple negative breast cancer |
| topic | antimetabolites isoselenocyanate 5-fluorouracil sulforaphane anticancer effect |
| url | https://www.mdpi.com/1420-3049/28/15/5808 |
| work_keys_str_mv | AT małgorzatamilczarek anorganofluorineisoselenocyanateanalogueofsulforaphaneaffectsantimetabolite5fluorouracilsanticanceractivityaperspectivefornewcombinatorytherapyintriplenegativebreastcancer AT tomaszcierpiał anorganofluorineisoselenocyanateanalogueofsulforaphaneaffectsantimetabolite5fluorouracilsanticanceractivityaperspectivefornewcombinatorytherapyintriplenegativebreastcancer AT piotrkiełbasinski anorganofluorineisoselenocyanateanalogueofsulforaphaneaffectsantimetabolite5fluorouracilsanticanceractivityaperspectivefornewcombinatorytherapyintriplenegativebreastcancer AT milenamałeckagiełdowska anorganofluorineisoselenocyanateanalogueofsulforaphaneaffectsantimetabolite5fluorouracilsanticanceractivityaperspectivefornewcombinatorytherapyintriplenegativebreastcancer AT martaswitalska anorganofluorineisoselenocyanateanalogueofsulforaphaneaffectsantimetabolite5fluorouracilsanticanceractivityaperspectivefornewcombinatorytherapyintriplenegativebreastcancer AT joannawietrzyk anorganofluorineisoselenocyanateanalogueofsulforaphaneaffectsantimetabolite5fluorouracilsanticanceractivityaperspectivefornewcombinatorytherapyintriplenegativebreastcancer AT maciejmazur anorganofluorineisoselenocyanateanalogueofsulforaphaneaffectsantimetabolite5fluorouracilsanticanceractivityaperspectivefornewcombinatorytherapyintriplenegativebreastcancer AT katarzynawiktorska anorganofluorineisoselenocyanateanalogueofsulforaphaneaffectsantimetabolite5fluorouracilsanticanceractivityaperspectivefornewcombinatorytherapyintriplenegativebreastcancer AT małgorzatamilczarek organofluorineisoselenocyanateanalogueofsulforaphaneaffectsantimetabolite5fluorouracilsanticanceractivityaperspectivefornewcombinatorytherapyintriplenegativebreastcancer AT tomaszcierpiał organofluorineisoselenocyanateanalogueofsulforaphaneaffectsantimetabolite5fluorouracilsanticanceractivityaperspectivefornewcombinatorytherapyintriplenegativebreastcancer AT piotrkiełbasinski organofluorineisoselenocyanateanalogueofsulforaphaneaffectsantimetabolite5fluorouracilsanticanceractivityaperspectivefornewcombinatorytherapyintriplenegativebreastcancer AT milenamałeckagiełdowska organofluorineisoselenocyanateanalogueofsulforaphaneaffectsantimetabolite5fluorouracilsanticanceractivityaperspectivefornewcombinatorytherapyintriplenegativebreastcancer AT martaswitalska organofluorineisoselenocyanateanalogueofsulforaphaneaffectsantimetabolite5fluorouracilsanticanceractivityaperspectivefornewcombinatorytherapyintriplenegativebreastcancer AT joannawietrzyk organofluorineisoselenocyanateanalogueofsulforaphaneaffectsantimetabolite5fluorouracilsanticanceractivityaperspectivefornewcombinatorytherapyintriplenegativebreastcancer AT maciejmazur organofluorineisoselenocyanateanalogueofsulforaphaneaffectsantimetabolite5fluorouracilsanticanceractivityaperspectivefornewcombinatorytherapyintriplenegativebreastcancer AT katarzynawiktorska organofluorineisoselenocyanateanalogueofsulforaphaneaffectsantimetabolite5fluorouracilsanticanceractivityaperspectivefornewcombinatorytherapyintriplenegativebreastcancer |