The wedelolactone derivative inhibits estrogen receptor-mediated breast, endometrial, and ovarian cancer cells growth.

Defeng Xu,Lu-Min Chen,Chawnshang Chang,Tzu-Hua Lin,Max A Cheng,Shuyuan Yeh,Chiuan-Ren Yeh

doi:10.1155/2014/713263

Abstract

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.

Highlights

Breast, endometrial, and ovarian cancers are the three most common cancers among women in the United States and are the major causes of cancer related deaths in females
We further investigated the the effects of BTB on cell growth in the estrogen-stimulatory environment using estrogen receptor (ER)-positive versus ER-negative breast, endometrial, and ovarian cancer cell lines
As BTB belongs to the furanocoumarin family/group compound, which could possess the agonist or antagonist activity of ER, we first investigated the ability of BTB to regulate ER transactivation activity in the HEK 293 cells

Summary

Introduction

Endometrial, and ovarian cancers are the three most common cancers among women in the United States and are the major causes of cancer related deaths in females. The development of effective prevention strategies for breast, endometrial, and ovarian cancers is a paramount opportunity in the care of women at risk for those malignancies [1]. It is well established that estrogens play a fundamental role in promoting the growth and progression of ER-related cancer cells. This understanding and control of the ER pathways have led to the development of various endocrine therapies by blocking estrogen-mediated tumor growth and progression

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Conclusion