Decursin and decursinol angelate inhibit estrogen-stimulated and estrogen-independent growth and survival of breast cancer cells

Cheng Jiang, Junming Guo, Zhe Wang, Bingxiu Xiao, Hyo Jung Lee, Eun Ok Lee, Sung Hoon Kim, Junxuan Lu

Research output: Contribution to journalArticle

64 Citations (Scopus)

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 ERα and ERβ 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 G 1 arrest and caspase-mediated apoptosis. These compounds decreased ERα 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 G 1 and G 2 phases as well as inducing apoptosis, accompanied by an increased expression of ERβ. 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.

Original languageEnglish (US)
Article numberR77
JournalBreast Cancer Research
Volume9
Issue number6
DOIs
StatePublished - Nov 6 2007

Fingerprint

Estrogens
Breast Neoplasms
Estrogen Receptors
Survival
Growth
MCF-7 Cells
Apoptosis
decursin
Pyranocoumarins
Androgen Antagonists
Caspase 1
Estrogen Receptor Modulators
Steroid Receptors
Androgen Receptors
Structure-Activity Relationship
Cell Cycle Checkpoints
Biological Products
Animal Models
Cell Line
Messenger RNA

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Jiang, Cheng ; Guo, Junming ; Wang, Zhe ; Xiao, Bingxiu ; Lee, Hyo Jung ; Lee, Eun Ok ; Kim, Sung Hoon ; Lu, Junxuan. / Decursin and decursinol angelate inhibit estrogen-stimulated and estrogen-independent growth and survival of breast cancer cells. In: Breast Cancer Research. 2007 ; Vol. 9, No. 6.
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title = "Decursin and decursinol angelate inhibit estrogen-stimulated and estrogen-independent growth and survival of breast cancer cells",
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 ERα and ERβ 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 G 1 arrest and caspase-mediated apoptosis. These compounds decreased ERα 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 G 1 and G 2 phases as well as inducing apoptosis, accompanied by an increased expression of ERβ. 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.",
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Decursin and decursinol angelate inhibit estrogen-stimulated and estrogen-independent growth and survival of breast cancer cells. / Jiang, Cheng; Guo, Junming; Wang, Zhe; Xiao, Bingxiu; Lee, Hyo Jung; Lee, Eun Ok; Kim, Sung Hoon; Lu, Junxuan.

In: Breast Cancer Research, Vol. 9, No. 6, R77, 06.11.2007.

Research output: Contribution to journalArticle

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 - 2007/11/6

Y1 - 2007/11/6

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 ERα and ERβ 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 G 1 arrest and caspase-mediated apoptosis. These compounds decreased ERα 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 G 1 and G 2 phases as well as inducing apoptosis, accompanied by an increased expression of ERβ. 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.

AB - 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 ERα and ERβ 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 G 1 arrest and caspase-mediated apoptosis. These compounds decreased ERα 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 G 1 and G 2 phases as well as inducing apoptosis, accompanied by an increased expression of ERβ. 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.

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