tectoridin and Breast-Neoplasms

Phytoestrogens are the natural compounds isolated from plants, which are structurally similar to animal estrogen, 17beta-estradiol. Tectoridin, a major isoflavone isolated from the rhizome of Belamcanda chinensis. Tectoridin is known as a phytoestrogen, however, the molecular mechanisms underlying its estrogenic effect are remained unclear. In this study we investigated the estrogenic signaling triggered by tectoridin as compared to a famous phytoestrogen, genistein in MCF-7 human breast cancer cells. Tectoridin scarcely binds to ER alpha as compared to 17beta-estradiol and genistein. Despite poor binding to ER alpha, tectoridin induced potent estrogenic effects, namely recovery of the population of cells in the S-phase after serum starvation, transactivation of the estrogen response element, and induction of MCF-7 cell proliferation. The tectoridin-induced estrogenic effect was severely abrogated by treatment with U0126, a specific MEK1/2 inhibitor. Tectoridin promoted phosphorylation of ERK1/2, but did not affect phosphorylation of ER alpha at Ser(118). It also increased cellular accumulation of cAMP, a hallmark of GPR30-mediated estrogen signaling. These data imply that tectoridin exerts its estrogenic effect mainly via the GPR30 and ERK-mediated rapid nongenomic estrogen signaling pathway. This property of tectoridin sets it aside from genistein where it exerts the estrogenic effects via both an ER-dependent genomic pathway and a GPR30-dependent nongenomic pathway.

Topics: Adenocarcinoma; Breast Neoplasms; Butadienes; Cell Line, Tumor; Cyclic AMP; Drug Interactions; Estradiol; Estrogen Receptor alpha; Female; Genistein; Humans; Isoflavones; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Nitriles; Phosphorylation; Phytoestrogens; Signal Transduction

From the rhizomes of Belamcanda chinensis, three new compounds, belalloside A (1), belalloside B (2), and belamphenone (3), along with 13 known compounds, resveratrol (4), iriflophenone (5), irisflorentin (6), tectorigenin (7), irilin D (8), tectoridin (9), iristectorin A (10), iristectorin B (11), hispiduloside, androsin, irigenin, iridin, and jaceoside, have been isolated and characterized. Isolates were evaluated for their cell proliferation stimulatory activity against the MCF-7 and T-47D human breast cancer cell lines. Along with 4, 5, 7, and 9, 3 was shown to stimulate not only MCF-7 but also T-47D human breast cancer cell proliferation.

Topics: Breast Neoplasms; Cell Proliferation; Female; Humans; Iridaceae; Isoflavones; Molecular Structure; Phenols; Plants, Medicinal; Resveratrol; Rhizome; Stilbenes; Thailand; Tumor Cells, Cultured