The Wedelolactone Derivative Inhibits Estrogen Receptor-Mediated Breast, Endometrial, and Ovarian Cancer Cells Growth

• Published in: BioMed research international Vol. 2014; no. 2014; pp. 1 - 11
• Main Authors: Lin, Tzu-Hua, Xu, Defeng, Yeh, Chiuan-Ren, Cheng, Max A., Chen, Lu-Min, Chang, Chawnshang, Yeh, Shuyuan
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Puplishing Corporation 01.01.2014; Hindawi Publishing Corporation; Hindawi Limited
• Subjects: Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cell growth; Cell Proliferation - drug effects; Coumarins - administration & dosage; Cyclin D1 - genetics; Cyclin D1 - metabolism; Endometrial Neoplasms - drug therapy; Endometrial Neoplasms - genetics; Endometrial Neoplasms - pathology; Estradiol - administration & dosage; Estrogen Receptor alpha - antagonists & inhibitors; Estrogen Receptor alpha - metabolism; Estrogens; Female; Gene Expression Regulation, Neoplastic; Humans; Kinases; MCF-7 Cells; Medical research; Ovarian cancer; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - genetics; Ovarian Neoplasms - pathology; Signal Transduction - drug effects
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2014/713263

Estrogen and estrogen receptor (ER)-mediated signaling pathways play important roles in the etiology and progression of human breast, endometrial, and ovarian cancers. Attenuating ER activities by natural products and their derivatives is a relatively practical strategy to control and reduce breast, endometrial, and ovarian cancer risk. Here, we found 3-butoxy-1,8,9-trihydroxy-6H-benzofuro[3,2-c]benzopyran-6-one (BTB), a new derivative of wedelolactone, could effectively inhibit the 17-estradiol (E2)-induced ER transactivation and suppress the growth of breast cancer as well as endometrial and ovarian cancer cells. Our results indicate that 2.5 μM BTB effectively suppresses ER-positive, but not ER-negative, breast, endometrial, and ovarian cancer cells. Furthermore, our data indicate that BTB can modulate ER transactivation and suppress the expression of E2-mediated ER target genes (Cyclin D1, E2F1, and TERT) in the ER-positive MCF-7, Ishikawa, and SKOV-3 cells. Importantly, this BTB mediated inhibition of ER activity is selective since BTB does not suppress the activities of other nuclear receptors, including glucocorticoid receptor and progesterone receptor, suggesting that BTB functions as a selective ER signaling inhibitor with the potential to treat breast, endometrial, and ovarian cancers.