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Decursin and decursinol angelate inhibit estrogen-stimulated and estrogen-independent growth and survival of breast cancer cells.
Breast Cancer Res. 2007; 9(6):R77.BC

Abstract

INTRODUCTION

Estrogen and estrogen receptor (ER)-mediated signaling are crucial for the etiology and progression of human breast cancer. Attenuating ER activities by natural products is a promising strategy to decrease breast cancer risk. We recently discovered that the pyranocoumarin compound decursin and its isomer decursinol angelate (DA) have potent novel antiandrogen receptor signaling activities. Because the ER and the androgen receptor belong to the steroid receptor superfamily, we examined whether these compounds affected ER expression and signaling in breast cancer cells.

METHODS

We treated estrogen-dependent MCF-7 and estrogen-independent MDA MB-231 human breast cancer cells with decursin and DA, and examined cell growth, apoptosis, and ERalpha and ERbeta expression in both cell lines - and, in particular, estrogen-stimulated signaling in the MCF-7 cells. We compared these compounds with decursinol to determine their structure-activity relationship.

RESULTS

Decursin and DA exerted growth inhibitory effects on MCF-7 cells through G1 arrest and caspase-mediated apoptosis. These compounds decreased ERalpha in MCF-7 cells at both mRNA and protein levels, and suppressed estrogen-stimulated genes. Decursin and the pure antiestrogen Faslodex exerted an additive growth inhibitory effect on MCF-7 cells. In MDA MB-231 cells, these compounds induced cell-cycle arrests in the G1 and G2 phases as well as inducing apoptosis, accompanied by an increased expression of ERbeta. In contrast, decursinol, which lacks the side chain of decursin and DA, did not have these cellular and molecular activities at comparable concentrations.

CONCLUSION

The side chain of decursin and DA is crucial for their anti-ER signaling and breast cancer growth inhibitory activities. These data provide mechanistic rationales for validating the chemopreventive and therapeutic efficacy of decursin and its derivatives in preclinical animal models of breast cancer.

Authors+Show Affiliations

The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17986353

Citation

Jiang, Cheng, et al. "Decursin and Decursinol Angelate Inhibit Estrogen-stimulated and Estrogen-independent Growth and Survival of Breast Cancer Cells." Breast Cancer Research : BCR, vol. 9, no. 6, 2007, pp. R77.
Jiang C, Guo J, Wang Z, et al. Decursin and decursinol angelate inhibit estrogen-stimulated and estrogen-independent growth and survival of breast cancer cells. Breast Cancer Res. 2007;9(6):R77.
Jiang, C., Guo, J., Wang, Z., Xiao, B., Lee, H. J., Lee, E. O., Kim, S. H., & Lu, J. (2007). Decursin and decursinol angelate inhibit estrogen-stimulated and estrogen-independent growth and survival of breast cancer cells. Breast Cancer Research : BCR, 9(6), R77.
Jiang C, et al. Decursin and Decursinol Angelate Inhibit Estrogen-stimulated and Estrogen-independent Growth and Survival of Breast Cancer Cells. Breast Cancer Res. 2007;9(6):R77. PubMed PMID: 17986353.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Decursin and decursinol angelate inhibit estrogen-stimulated and estrogen-independent growth and survival of breast cancer cells. AU - Jiang,Cheng, AU - Guo,Junming, AU - Wang,Zhe, AU - Xiao,Bingxiu, AU - Lee,Hyo-Jung, AU - Lee,Eun-Ok, AU - Kim,Sung-Hoon, AU - Lu,Junxuan, PY - 2007/04/16/received PY - 2007/08/07/revised PY - 2007/11/06/accepted PY - 2007/11/8/pubmed PY - 2008/3/7/medline PY - 2007/11/8/entrez SP - R77 EP - R77 JF - Breast cancer research : BCR JO - Breast Cancer Res VL - 9 IS - 6 N2 - INTRODUCTION: Estrogen and estrogen receptor (ER)-mediated signaling are crucial for the etiology and progression of human breast cancer. Attenuating ER activities by natural products is a promising strategy to decrease breast cancer risk. We recently discovered that the pyranocoumarin compound decursin and its isomer decursinol angelate (DA) have potent novel antiandrogen receptor signaling activities. Because the ER and the androgen receptor belong to the steroid receptor superfamily, we examined whether these compounds affected ER expression and signaling in breast cancer cells. METHODS: We treated estrogen-dependent MCF-7 and estrogen-independent MDA MB-231 human breast cancer cells with decursin and DA, and examined cell growth, apoptosis, and ERalpha and ERbeta expression in both cell lines - and, in particular, estrogen-stimulated signaling in the MCF-7 cells. We compared these compounds with decursinol to determine their structure-activity relationship. RESULTS: Decursin and DA exerted growth inhibitory effects on MCF-7 cells through G1 arrest and caspase-mediated apoptosis. These compounds decreased ERalpha in MCF-7 cells at both mRNA and protein levels, and suppressed estrogen-stimulated genes. Decursin and the pure antiestrogen Faslodex exerted an additive growth inhibitory effect on MCF-7 cells. In MDA MB-231 cells, these compounds induced cell-cycle arrests in the G1 and G2 phases as well as inducing apoptosis, accompanied by an increased expression of ERbeta. In contrast, decursinol, which lacks the side chain of decursin and DA, did not have these cellular and molecular activities at comparable concentrations. CONCLUSION: The side chain of decursin and DA is crucial for their anti-ER signaling and breast cancer growth inhibitory activities. These data provide mechanistic rationales for validating the chemopreventive and therapeutic efficacy of decursin and its derivatives in preclinical animal models of breast cancer. SN - 1465-542X UR - https://www.unboundmedicine.com/medline/citation/17986353/Decursin_and_decursinol_angelate_inhibit_estrogen_stimulated_and_estrogen_independent_growth_and_survival_of_breast_cancer_cells_ L2 - https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr1790 DB - PRIME DP - Unbound Medicine ER -