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

Xu D, Lin TH, Yeh CR, Cheng MA, Chen LM, Chang C, Yeh S - Biomed Res Int (2014)

Bottom Line: Estrogen and estrogen receptor (ER)-mediated signaling pathways play important roles in the etiology and progression of human breast, endometrial, and ovarian cancers.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.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmaceutical and Life Sciences, Changzhou University, Changzhou, Jiangsu 213164, China ; George H. Whipple Laboratory for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.

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.

Show MeSH

Related in: MedlinePlus

Differential growth inhibition effects of BTB on ERα-positive versus ERα-negative breast, endometrial, and ovary cancer cell lines. Cells were treated with 2.5 μM BTB or mock EtOH in the absence or presence of 10 nM E2. Phenol red free DMEM medium with indicated treatment was refreshed every 2 days for a total of 6 days. (a)–(c) BTB Inhibits the E2-induced growth of ER-positive breast cancer MCF-7, endometrial cancer Ishikawa, and ovarian cancer SKOV-3 cells. (d)–(f) BTB has no effect on the growth of ER-negative breast cancer MDA-MB-231, endometrial cancer HEC-1-A, and ovarian cancer OVCA429 cells. Data represent mean ± SD collected from three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC4157183&req=5

fig2: Differential growth inhibition effects of BTB on ERα-positive versus ERα-negative breast, endometrial, and ovary cancer cell lines. Cells were treated with 2.5 μM BTB or mock EtOH in the absence or presence of 10 nM E2. Phenol red free DMEM medium with indicated treatment was refreshed every 2 days for a total of 6 days. (a)–(c) BTB Inhibits the E2-induced growth of ER-positive breast cancer MCF-7, endometrial cancer Ishikawa, and ovarian cancer SKOV-3 cells. (d)–(f) BTB has no effect on the growth of ER-negative breast cancer MDA-MB-231, endometrial cancer HEC-1-A, and ovarian cancer OVCA429 cells. Data represent mean ± SD collected from three independent experiments.

Mentions: As BTB could selectively inhibit the ER-mediated transactivation, we then investigated the effects of BTB on the inhibition of E2-induced cell proliferation in ER-positive MCF7, Ishikawa, and SKOV-3 cancer cells and compared this with the ER-negative MDA-MB-231, HEC-1-A, and OVCA429 cancer cells. BTB reduced E2-induced cell growth in MCF-7, Ishikawa, and SKOV-3 cells by 50%, 55%, and 62%, respectively (Figures 2(a)–2(c)). As shown in Figure 1, 2.5 μM BTB treatment could not completely block E2-induced ER transactivation on ERE-luciferase; we did not expect to see 100% completion of E2 stimulated growth. On the other hand, BTB failed to inhibit the growth of those three ER-negative cancer cell lines in the presence or in the absence of E2 (Figures 2(d) and 2(f)).


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

Xu D, Lin TH, Yeh CR, Cheng MA, Chen LM, Chang C, Yeh S - Biomed Res Int (2014)

Differential growth inhibition effects of BTB on ERα-positive versus ERα-negative breast, endometrial, and ovary cancer cell lines. Cells were treated with 2.5 μM BTB or mock EtOH in the absence or presence of 10 nM E2. Phenol red free DMEM medium with indicated treatment was refreshed every 2 days for a total of 6 days. (a)–(c) BTB Inhibits the E2-induced growth of ER-positive breast cancer MCF-7, endometrial cancer Ishikawa, and ovarian cancer SKOV-3 cells. (d)–(f) BTB has no effect on the growth of ER-negative breast cancer MDA-MB-231, endometrial cancer HEC-1-A, and ovarian cancer OVCA429 cells. Data represent mean ± SD collected from three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4157183&req=5

fig2: Differential growth inhibition effects of BTB on ERα-positive versus ERα-negative breast, endometrial, and ovary cancer cell lines. Cells were treated with 2.5 μM BTB or mock EtOH in the absence or presence of 10 nM E2. Phenol red free DMEM medium with indicated treatment was refreshed every 2 days for a total of 6 days. (a)–(c) BTB Inhibits the E2-induced growth of ER-positive breast cancer MCF-7, endometrial cancer Ishikawa, and ovarian cancer SKOV-3 cells. (d)–(f) BTB has no effect on the growth of ER-negative breast cancer MDA-MB-231, endometrial cancer HEC-1-A, and ovarian cancer OVCA429 cells. Data represent mean ± SD collected from three independent experiments.
Mentions: As BTB could selectively inhibit the ER-mediated transactivation, we then investigated the effects of BTB on the inhibition of E2-induced cell proliferation in ER-positive MCF7, Ishikawa, and SKOV-3 cancer cells and compared this with the ER-negative MDA-MB-231, HEC-1-A, and OVCA429 cancer cells. BTB reduced E2-induced cell growth in MCF-7, Ishikawa, and SKOV-3 cells by 50%, 55%, and 62%, respectively (Figures 2(a)–2(c)). As shown in Figure 1, 2.5 μM BTB treatment could not completely block E2-induced ER transactivation on ERE-luciferase; we did not expect to see 100% completion of E2 stimulated growth. On the other hand, BTB failed to inhibit the growth of those three ER-negative cancer cell lines in the presence or in the absence of E2 (Figures 2(d) and 2(f)).

Bottom Line: Estrogen and estrogen receptor (ER)-mediated signaling pathways play important roles in the etiology and progression of human breast, endometrial, and ovarian cancers.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.

View Article: PubMed Central - PubMed

Affiliation: School of Pharmaceutical and Life Sciences, Changzhou University, Changzhou, Jiangsu 213164, China ; George H. Whipple Laboratory for Cancer Research, Departments of Urology and Pathology, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA.

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.

Show MeSH
Related in: MedlinePlus