The nutritional herb Epimedium grandiflorum inhibits the growth in a model for the Luminal A molecular subtype of breast cancer
Autor: | Gou Li, George Y. Wong, H. Leon Bradlow, Meena Katdare, Nitin T. Telang, Daniel W. Sepkovic |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Cancer Research Oncogene Estrogen receptor Cancer Cell cycle Biology Pharmacology medicine.disease_cause medicine.disease 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Breast cancer Oncology Selective estrogen receptor modulator 030220 oncology & carcinogenesis Progesterone receptor medicine Carcinogenesis |
Zdroj: | Oncology Letters. 13:2477-2482 |
ISSN: | 1792-1082 1792-1074 |
Popis: | The Luminal A subtype of breast cancer expresses the estrogen receptor (ER)-α and progesterone receptor (PR), but not the human epidermal growth factor receptor (HER)-2 oncogene. This subtype of breast cancer responds to endocrine therapy involving the use of selective estrogen receptor modulators and/or inhibitors of estrogen biosynthesis. However, these therapeutic agents are frequently associated with long-term systemic toxicity and acquired tumor resistance, emphasizing the need to identify non-toxic alternative treatments for chemo-endocrine therapy responsive breast cancer. The present study utilized the human mammary carcinoma-derived, ER+/PR+/HER-2- MCF-7 cell line as a model of the Luminal A subtype of breast cancer to examine the growth inhibitory effect of the Chinese nutritional herb Epimedium grandiflorum (EG) and determine the mechanisms underlying this effect. MCF-7 cells maintained in a serum-depleted culture medium retained their ability to grow in response to 17β-estradiol (E2). Treatment of the MCF-7 cells with EG resulted in dose-dependent inhibition of E2-promoted growth. Mechanistically, EG inhibited E2-promoted cell cycle progression through G1 stage arrest and modulated the cellular metabolism of E2, increasing the formation of the anti-proliferative metabolites 2-hydroxyestrone and estriol. Long-term treatment of MCF-7 cells with EG inhibited E2-promoted anchorage independent growth, a surrogate in vitro biomarker of tumorigenesis. In conclusion, the results of the present study demonstrate the growth inhibitory effects of EG on MCF-7 cells and identified clinically relevant mechanistic leads for its anti-tumorigenic efficacy. |
Databáze: | OpenAIRE |
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