Antiestrogenic and antiproliferative potency of secoisolariciresinol diglucoside derivatives on MCF-7 breast cancer cells

Abstract

Secoisolariciresinol diglucoside (SDG) is isolated from Linum usitatissimum seeds. The antiproliferative effects of SDG (1) and its derivatives secoisolariciresinol (2) and secoisolariciresinol-4′, 4″-diacetate (3) have been evaluated on MCF-7 breast cancer cells and normal breast epithelial line MCF-10A. Lignan 1 has not shown cytotoxic effects on MCF-7 cells, while derivatives 2 and 3 have inhibited cell growth with IC₅₀ values of 25 and 11 µM, respectively. Estrogen receptor alpha is a key growth driver in MCF-7 cells. Compound 1 did not affect the activity of ERα, while derivatives 2 and 3 showed significant antiestrogenic effects. Compounds 2 and 3 caused apoptosis in the MCF-7 line, determined by the cleavage of PARP. SDG derivative 3 enhanced the effect of doxorubicin. SDG derivatives can be considered as promising agents that exhibit a combined antiestrogen and proapoptotic effect in hormone-dependent breast cancer cells.

Keywords:

• Lignans
• secoisolariciresinol diglucoside
• derivatives
• secoisolariciresinol
• secoisolariciresinol-4′, 4″-diacetate
• breast cancer cells
• apoptosis
• cytotoxicity
• estrogen receptor

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The st

udy was financially supported by the Russian Foundation for Basic Research, project 18-29-09017 (ERE-Luc assays and experiments with MCF-10A cells). Special thanks to Dr. Irina Stasevich for the inspiring discussion at the 8th EACR-OECI Joint Course: Molecular Pathology Approach to Cancer held at De Rode Hoed near beautiful canals of Amsterdam. The densitometry protocol for immunoblotting “Using ImageJ to quantify blots” was provided by The University of Queensland (https://di.uq.edu.au/community-and-alumni/sparq-ed/sparq-ed-services/using-imagej-quantify-blots). The authors thank Aglaya Shcherbakova for her kind help in the design of graphical abstract. Graphical abstract was created using Servier Medical Art templates. Original templates are licensed under a Creative Commons Attribution 3.0 Unported License (https://smart.servier.com/).