Endocrine Abstracts

We previously reported that calycosin, a natural phytoestrogen structurally similar to estrogen, successfully triggered apoptosis of ER-positive breast cancer cell line, MCF-7. To better understand the antitumor activities of calycosin against breast cancer, besides MCF-7 cells, another ER-positive cell line T-47D was analyzed here, with ER-negative cell lines (MDA-231 and MDA-435) as control. Notably, calycosin led to inhibited cell viability and apoptosis only in ER-positive cells, particularly in MCF-7 cells, but no such effect was observed in ER-negative cells. Thus MCF-7 cells were chosen to further identify the possible link between calycosin and ER signaling. After the treatment of calycosin, the expression levels of ER β (ERβ) were greatly increased in MCF-7 cells, whereas the expression of ER α (ERα) remained relatively constant. Moreover, accompanied by upregulation of ERβ, successive changes in downstream signaling pathways were found, including inactivation of IGF-1R, then stimulation of p38 MAPK and suppression of the serine/threonine kinase (Akt), and finally poly(ADP-ribose) polymerase 1 (PARP-1) cleavage. However, the other two members of the MAPK family, extracellular signal-regulated kinase (ERK) 1/2 and c-Jun N-terminal kinase (JNK), were not consequently regulated by downregulated IGF-1R, indicating ERK 1/2 and JNK pathways were not necessary to allow proliferation inhibition by calycosin. Taken together, our results indicate that calycosin tends to inhibit growth and induce apoptosis in ER-positive breast cancer cells, which is mediated by ERβ-induced inhibition of IGF-1R, along with the selective regulation of MAPK and phosphatidylinositol 3-kinase (PI3K)/Akt pathways.