In the triple-negative breast cancer MDA-MB-231 cell line, sulforaphane enhances the intracellular accumulation and anticancer action of doxorubicin encapsulated in liposomes

Lidia Mielczarek; Pamela Krug; Maciej Mazur; Małgorzata Milczarek; Zdzisław Chilmonczyk; Katarzyna Wiktorska

doi:10.1016/j.ijpharm.2019.01.008

In the triple-negative breast cancer MDA-MB-231 cell line, sulforaphane enhances the intracellular accumulation and anticancer action of doxorubicin encapsulated in liposomes

Int J Pharm. 2019 Mar 10:558:311-318. doi: 10.1016/j.ijpharm.2019.01.008. Epub 2019 Jan 12.

Authors

Lidia Mielczarek¹, Pamela Krug², Maciej Mazur³, Małgorzata Milczarek⁴, Zdzisław Chilmonczyk⁴, Katarzyna Wiktorska⁵

Affiliations

¹ Department of Drug Biotechnology and Bioinformatics, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland; Department of Drug Analysis, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warsaw, Poland.
² Department of Drug Biotechnology and Bioinformatics, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland; Department of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland.
³ Department of Chemistry, University of Warsaw, Pasteura 1, 02-093 Warsaw, Poland.
⁴ Department of Drug Biotechnology and Bioinformatics, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland.
⁵ Department of Drug Biotechnology and Bioinformatics, National Medicines Institute, Chełmska 30/34, 00-725 Warsaw, Poland. Electronic address: k.wiktorska@nil.gov.pl.

PMID: 30641176
DOI: 10.1016/j.ijpharm.2019.01.008

Abstract

A new combination of sulforaphane (a natural compound obtained from Brassicaceae vegetables) and the cytostatic drug doxorubicin was entrapped in nanometer-sized liposomes. In vitro experiments were performed to investigate the cytotoxicity of these structures on the human breast cancer cell line MDA-MB-231. Confocal microscopy studies revealed enhanced cellular endocytotic internalization, followed by the release of the examined combination from the lysosomes. The in vitro interaction analysis using the Chou-Talalay approach showed high synergistic activity of the examined combination. This synergistic activity enables a considerable reduction in cytostatic dosage and an increase in cancer treatment efficiency.

Keywords: Breast cancer; Doxorubicin; Intracellular distribution; Liposomes; Sulforaphane; Synergy.

MeSH terms

Antibiotics, Antineoplastic / administration & dosage*
Anticarcinogenic Agents / administration & dosage*
Antineoplastic Combined Chemotherapy Protocols
Cell Line, Tumor
Cell Survival / drug effects
Doxorubicin / administration & dosage*
Drug Synergism
Female
Humans
Isothiocyanates / administration & dosage*
Liposomes
Sulfoxides
Triple Negative Breast Neoplasms / drug therapy*

Substances

Antibiotics, Antineoplastic
Anticarcinogenic Agents
Isothiocyanates
Liposomes
Sulfoxides
Doxorubicin
sulforaphane