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.

摘要

Secoisolariciresinol diglucoside (SDG) 是从亚麻籽中分离出来的。SDG (1)及其衍生物 secoisolariciresinol (2)和 secoisolariciresinol-4', 4"-diacetate ( 3)对 MCF-7 乳腺癌细胞和正常乳腺上皮细胞系 MCF-10A的抗增殖作用进行了评估。木酚素1未显示对 MCF-7 细胞的细胞毒性作用，而衍生物2和3抑制细胞生长，IC ₅₀值分别为 25 和 11 µM。雌激素受体 α 是 MCF-7 细胞的关键生长驱动因素。化合物1不影响 ERα 的活性，而衍生物2和3显示出显着的抗雌激素作用。化合物2和3在 MCF-7 系中引起细胞凋亡，这由 PARP 的裂解决定。SDG 衍生物3增强了阿霉素的作用。SDG 衍生物可以被认为是有前途的药物，在激素依赖性乳腺癌细胞中表现出联合抗雌激素和促凋亡作用。