Potent antiandrogen and androgen receptor activities of an Angelica gigas-containing herbal formulation: Identification of decursin as a novel and active compound with implications for prevention and treatment of prostate cancer

Cheng Jiang, Hyo Jeong Lee, Guang Xun Li, Junming Guo, Barbara Malewicz, Yan Zhao, Eun Ok Lee, Hyo Jung Lee, Jae Ho Lee, Min Seok Kim, Sung Hoon Kim, Junxuan Lu

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Androgen and androgen receptor (AR)-mediated signaling are crucial for the development of prostate cancer. Identification of novel and naturally occurring phytochemicals that target androgen and AR signaling from Oriental medicinal herbs holds exciting promises for the chemoprevention of this disease. In this article, we report the discovery of strong and long-lasting antiandrogen and AR activities of the ethanol extract of a herbal formula (termed KMKKT) containing Korean Angelica gigas Nakai (AGN) root and nine other Oriental herbs in the androgen-dependent LNCaP human prostate cancer cell model. The functional biomarkers evaluated included a suppression of the expression of prostate-specific antigen (PSA) mRNA and protein (IC50, ∼7 μg/mL, 48-hour exposure) and an inhibition of androgen-induced cell proliferation through G1 arrest and of the ability of androgen to suppress neuroendocrine differentiation at exposure concentrations that did not cause apoptosis. Through activity-guided fractionation, we identified decursin from AGN as a novel antiandrogen and AR compound with an IC50 of ∼0.4 μg/mL (1.3 μmol/L, 48-hour exposure) for suppressing PSA expression. Decursin also recapitulated the neuroendocrine differentiation induction and G1 arrest actions of the AGN and KMKKT extracts. Mechanistically, decursin in its neat form or as a component of AGN or KMKKT extracts inhibited androgen-stimulated AR translocation to the nucleus and down-regulated AR protein abundance without affecting the AR mRNA level. The novel antiandrogen and AR activities of decursin and decursin-containing herbal extracts have significant implications for the chemoprevention and treatment of prostate cancer and other androgen-dependent diseases.

Original languageEnglish (US)
Pages (from-to)453-463
Number of pages11
JournalCancer Research
Volume66
Issue number1
DOIs
StatePublished - Jan 1 2006

Fingerprint

Angelica
Androgen Antagonists
Androgen Receptors
Prostatic Neoplasms
Androgens
Chemoprevention
Therapeutics
Prostate-Specific Antigen
Inhibitory Concentration 50
Messenger RNA
decursin
Phytochemicals
Medicinal Plants
Proteins
Ethanol
Biomarkers
Cell Proliferation
Apoptosis

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Jiang, Cheng ; Lee, Hyo Jeong ; Li, Guang Xun ; Guo, Junming ; Malewicz, Barbara ; Zhao, Yan ; Lee, Eun Ok ; Lee, Hyo Jung ; Lee, Jae Ho ; Kim, Min Seok ; Kim, Sung Hoon ; Lu, Junxuan. / Potent antiandrogen and androgen receptor activities of an Angelica gigas-containing herbal formulation : Identification of decursin as a novel and active compound with implications for prevention and treatment of prostate cancer. In: Cancer Research. 2006 ; Vol. 66, No. 1. pp. 453-463.
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abstract = "Androgen and androgen receptor (AR)-mediated signaling are crucial for the development of prostate cancer. Identification of novel and naturally occurring phytochemicals that target androgen and AR signaling from Oriental medicinal herbs holds exciting promises for the chemoprevention of this disease. In this article, we report the discovery of strong and long-lasting antiandrogen and AR activities of the ethanol extract of a herbal formula (termed KMKKT) containing Korean Angelica gigas Nakai (AGN) root and nine other Oriental herbs in the androgen-dependent LNCaP human prostate cancer cell model. The functional biomarkers evaluated included a suppression of the expression of prostate-specific antigen (PSA) mRNA and protein (IC50, ∼7 μg/mL, 48-hour exposure) and an inhibition of androgen-induced cell proliferation through G1 arrest and of the ability of androgen to suppress neuroendocrine differentiation at exposure concentrations that did not cause apoptosis. Through activity-guided fractionation, we identified decursin from AGN as a novel antiandrogen and AR compound with an IC50 of ∼0.4 μg/mL (1.3 μmol/L, 48-hour exposure) for suppressing PSA expression. Decursin also recapitulated the neuroendocrine differentiation induction and G1 arrest actions of the AGN and KMKKT extracts. Mechanistically, decursin in its neat form or as a component of AGN or KMKKT extracts inhibited androgen-stimulated AR translocation to the nucleus and down-regulated AR protein abundance without affecting the AR mRNA level. The novel antiandrogen and AR activities of decursin and decursin-containing herbal extracts have significant implications for the chemoprevention and treatment of prostate cancer and other androgen-dependent diseases.",
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Potent antiandrogen and androgen receptor activities of an Angelica gigas-containing herbal formulation : Identification of decursin as a novel and active compound with implications for prevention and treatment of prostate cancer. / Jiang, Cheng; Lee, Hyo Jeong; Li, Guang Xun; Guo, Junming; Malewicz, Barbara; Zhao, Yan; Lee, Eun Ok; Lee, Hyo Jung; Lee, Jae Ho; Kim, Min Seok; Kim, Sung Hoon; Lu, Junxuan.

In: Cancer Research, Vol. 66, No. 1, 01.01.2006, p. 453-463.

Research output: Contribution to journalArticle

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T1 - Potent antiandrogen and androgen receptor activities of an Angelica gigas-containing herbal formulation

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AU - Jiang, Cheng

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AU - Guo, Junming

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AU - Zhao, Yan

AU - Lee, Eun Ok

AU - Lee, Hyo Jung

AU - Lee, Jae Ho

AU - Kim, Min Seok

AU - Kim, Sung Hoon

AU - Lu, Junxuan

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N2 - Androgen and androgen receptor (AR)-mediated signaling are crucial for the development of prostate cancer. Identification of novel and naturally occurring phytochemicals that target androgen and AR signaling from Oriental medicinal herbs holds exciting promises for the chemoprevention of this disease. In this article, we report the discovery of strong and long-lasting antiandrogen and AR activities of the ethanol extract of a herbal formula (termed KMKKT) containing Korean Angelica gigas Nakai (AGN) root and nine other Oriental herbs in the androgen-dependent LNCaP human prostate cancer cell model. The functional biomarkers evaluated included a suppression of the expression of prostate-specific antigen (PSA) mRNA and protein (IC50, ∼7 μg/mL, 48-hour exposure) and an inhibition of androgen-induced cell proliferation through G1 arrest and of the ability of androgen to suppress neuroendocrine differentiation at exposure concentrations that did not cause apoptosis. Through activity-guided fractionation, we identified decursin from AGN as a novel antiandrogen and AR compound with an IC50 of ∼0.4 μg/mL (1.3 μmol/L, 48-hour exposure) for suppressing PSA expression. Decursin also recapitulated the neuroendocrine differentiation induction and G1 arrest actions of the AGN and KMKKT extracts. Mechanistically, decursin in its neat form or as a component of AGN or KMKKT extracts inhibited androgen-stimulated AR translocation to the nucleus and down-regulated AR protein abundance without affecting the AR mRNA level. The novel antiandrogen and AR activities of decursin and decursin-containing herbal extracts have significant implications for the chemoprevention and treatment of prostate cancer and other androgen-dependent diseases.

AB - Androgen and androgen receptor (AR)-mediated signaling are crucial for the development of prostate cancer. Identification of novel and naturally occurring phytochemicals that target androgen and AR signaling from Oriental medicinal herbs holds exciting promises for the chemoprevention of this disease. In this article, we report the discovery of strong and long-lasting antiandrogen and AR activities of the ethanol extract of a herbal formula (termed KMKKT) containing Korean Angelica gigas Nakai (AGN) root and nine other Oriental herbs in the androgen-dependent LNCaP human prostate cancer cell model. The functional biomarkers evaluated included a suppression of the expression of prostate-specific antigen (PSA) mRNA and protein (IC50, ∼7 μg/mL, 48-hour exposure) and an inhibition of androgen-induced cell proliferation through G1 arrest and of the ability of androgen to suppress neuroendocrine differentiation at exposure concentrations that did not cause apoptosis. Through activity-guided fractionation, we identified decursin from AGN as a novel antiandrogen and AR compound with an IC50 of ∼0.4 μg/mL (1.3 μmol/L, 48-hour exposure) for suppressing PSA expression. Decursin also recapitulated the neuroendocrine differentiation induction and G1 arrest actions of the AGN and KMKKT extracts. Mechanistically, decursin in its neat form or as a component of AGN or KMKKT extracts inhibited androgen-stimulated AR translocation to the nucleus and down-regulated AR protein abundance without affecting the AR mRNA level. The novel antiandrogen and AR activities of decursin and decursin-containing herbal extracts have significant implications for the chemoprevention and treatment of prostate cancer and other androgen-dependent diseases.

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