Calycosin induces apoptosis by upregulation of RASD1 in human breast cancer cells MCF-7.

Abstract

Breast cancer is a leading cause of cancer death among women, and the failure of normal apoptosis has been proved in the development of breast cancer. The phytoestrogen, calycosin, is extracted from Chinese medical herb Radix astragali. We recently reported that calycosin successfully stimulated proliferation of ER-positive MCF-7 human breast cancer cells at low concentration. In the present study, we assessed the proapoptotic function of calycosin in MCF-7 cells at high concentration in vitro, as well as the possible mechanism of its effect. MCF-7 cells were treated with different concentrations of calycosin, and then detected by MTT assay for cellular viability, Hoechst assay, and flow cytometry for apoptosis. RASD1 is identified as a Ras-family member and a regulator in MAPK-mediated cascade leading to cell proliferation or apoptosis. To provide insight into the functions of RASD1 signaling pathway in calycosin-induced apoptosis, the expression of Bcl-2, Bax, and RASD1 in calycosin-treated cells were determined by Western blot assay. The results showed that high concentrations of calycosin significantly suppressed the proliferation of MCF-7 cells and promoted cell apoptosis. Moreover, compared with control group, the expression of Bcl-2 decreased with calycosin in MCF-7 cells, while Bax increased, which was significantly correlated with elevated expression of RASD1. Together, we present evidence that at relatively high concentration calycosin triggered cell apoptosis through the mitochondrial apoptotic pathway by upregulating RASD1. And for the first time, this study revealed that calycosin may have potential as a therapeutic agent for the treatment of breast cancer.

• Authors: J Tian, Y X Duan, C Y Bei, J Chen
• Journal: Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme (Horm Metab Res) Vol. 45 Issue 8 Pg. 593-8 (Aug 2013) ISSN: 1439-4286 [Electronic] Germany
• PMID: 23609007 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © Georg Thieme Verlag KG Stuttgart · New York.

Chemical References

• Isoflavones
• Proto-Oncogene Proteins c-bcl-2
• RASD1 protein, human
• bcl-2-Associated X Protein
• 7,3'-dihydroxy-4'-methoxyisoflavone
• ras Proteins

Topics

• Apoptosis (drug effects)
• Breast Neoplasms (drug therapy, genetics, metabolism, physiopathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Female
• Humans
• Isoflavones (pharmacology)
• Mitochondria (drug effects, metabolism)
• Proto-Oncogene Proteins c-bcl-2 (genetics, metabolism)
• Signal Transduction (drug effects)
• Up-Regulation (drug effects)
• bcl-2-Associated X Protein (genetics, metabolism)
• ras Proteins (genetics, metabolism)