Secoisolariciresinol diglucoside (SDG) is isolated from <i>Linum usitatissimum</i> seeds. The antiproliferative effects of SDG <b>(1)</b> and its derivatives secoisolariciresinol <b>(2)</b> and secoisolariciresinol-4', 4″-diacetate (<b>3)</b> have been evaluated on MCF-7 breast cancer cells and normal breast epithelial line MCF-10A. Lignan <b>1</b> has not shown cytotoxic effects on MCF-7 cells, while derivatives <b>2</b> and <b>3</b> 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 <b>1</b> did not affect the activity of ERα, while derivatives <b>2</b> and <b>3</b> showed significant antiestrogenic effects. Compounds <b>2</b> and <b>3</b> caused apoptosis in the MCF-7 line, determined by the cleavage of PARP. SDG derivative <b>3</b> 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; apoptosis; breast cancer cells; cytotoxicity; derivatives; estrogen receptor; secoisolariciresinol; secoisolariciresinol diglucoside; secoisolariciresinol-4′, 4″-diacetate.