Anti‐Androgen Effects of Extracts and Compounds from <i>Ganoderma lucidum</i>

Liu, Jie; Tamura, Sadaaki; Kurashiki, Kenji; Shimizu, Kuniyoshi; Noda, Kiyoshi; Konishi, Fumiko; Kumamoto, Shoichiro; Kondo, Ryuichiro

doi:10.1002/cbdv.200800019

Cited by 21 publications

(15 citation statements)

References 33 publications

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“…The 30% ethanol extracts were proved to inhibit the grown of LNCaP cells and some alcholic triterpene components of the extract, ganodierols A, B [89] and F Fig. (2) [90], showed binding activity to AR, and comparison of the efficacy of the triterpene components of the crude extract lead to draw some structure-activity relationship [91].…”

Section: Natural Androgen Receptor (Ar) Ligandsmentioning

confidence: 98%

Natural Ligands for Nuclear Receptors: Biology and Potential Therapeutic Applications

D’Auria¹,

Sepe²,

Zampella

2012

CTMC

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Nuclear receptors are key regulators of various processes including reproduction, development, and metabolism of xeno- and endobiotics. Research in the last two decades has focused to the development of novel drugs specifically targeting nuclear receptors for the treatment of a variety of diseases, such as cancer, diabetes, dyslipidemia, fatty liver disease, drug hepatotoxicity and cholestasis. The search for novel NRs agonists and antagonists with enhanced selectivity prompted the exploration of the extraordinary chemical diversity associated to natural products. In recent years a number of natural products were disclosed as ligands of NRs and proved to have remarkable affinity and in some cases peculiar mode of action. In this review the natural ligands of the subfamily NR1, NR2, and NR3 will be described with an emphasis to their mechanisms of action and pharmacological profiles.

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Section: Natural Androgen Receptor (Ar) Ligandsmentioning

confidence: 98%

Natural Ligands for Nuclear Receptors: Biology and Potential Therapeutic Applications

D’Auria¹,

Sepe²,

Zampella

2012

CTMC

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“…Our group previously isolated a series of triterpenoids from G. lingzhi . These compounds suppressed the proliferation of androgen-dependent and androgen-independent prostate cancer cell lines11 and estrogen-dependent MCF-7 cells12, and inhibited osteoclastic differentiation13. Among these triterpenoids, we found that only ganoderic acid DM ( 1 , Fig.…”

mentioning

confidence: 90%

“…Among these triterpenoids, we found that only ganoderic acid DM ( 1 , Fig. 1) had multiple functions, such as 5α-reductase inhibition, androgen receptor binding activity, prostate cancer cell, and proliferation and osteoclast differentiation11121314. Although 1 affects different signaling pathways in different cell lines and has multiple functions, we have identified its target proteins, which explain and clarify the universal mechanism of its medicinal efficacy.…”

mentioning

confidence: 92%

“…Dai et al8 proposed a new species Ganoderma lingzhi Sheng H. Wu, Y. Cao & Y. C. Dai for “Lingzhi”, which has an East Asia distribution. Considering the characteristics of Ganoderma mushroom used in our study, we herein revised the scientific name of used mushroom from ‘ G. lucidum ’ to ‘ G. lingzhi ’ although we described ‘ G. lucidum ’ in our all previous papers91011121314.…”

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confidence: 99%

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Target proteins of ganoderic acid DM provides clues to various pharmacological mechanisms

Liu

Shimizu

Tanaka

et al. 2012

Sci Rep

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Ganoderma fungus (Ganodermataceae) is a multifunctional medicinal mushroom and has been traditionally used for the treatment of various types of disease. Ganoderic acid DM (1) is a representative triterpenoid isolated from G. lingzhi and exhibits various biological activities. However, a universal starting point that triggers multiple signaling pathways and results in multifunctionality of 1 is unknown. Here we demonstrate the important clues regarding the mechanisms underlying multi-medicinal action of 1. We examined structure–activity relationships between 1 and its analogs and found that the carbonyl group at C-3 was essential for cytotoxicity. Subsequently, we used 1-conjugated magnetic beads as a probe and identified tubulin as a specific 1-binding protein. Furthermore, 1 showed a similar Kd to that of vinblastine and also affected assembly of tubulin polymers. This study revealed multiple biological activities of 1 and may contribute to the design and development of new tubulin-inhibiting agents.

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“…Also, treatment of the fruit body of G. lucidum itself or its ethanol extracts significantly inhibited the growth of the ventral prostate induced by testosterone in rats (13,14). Our group previously has obtained a series of triterpenoids from G. lucidum, which showed suppressive effects on the proliferation of the androgen-dependent or androgen-independent prostate cancer cell line (15), estrogen-like effects on the proliferation of the estrogen-dependent MCF-7 cells (16) and inhibitory effects on osteoclastic differentiation (17). Among all these triterpenoids, we found that only ganoderic acid DM (1, Fig.…”

Section: Introductionmentioning

confidence: 99%

A protocol for isolation of target proteins of natural compounds

Liu¹,

Shimizu²,

Tanaka³

et al. 2013

Protocol Exchange

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Target proteins are functional biomolecules that are addressed and controlled by biologically active compounds. The identification of target proteins is a key element of understanding molecular mechanism of action of ligands, since the interaction with target proteins is particular important for molecular biology, molecular pharmacy. To identify target proteins, new technologies are being developed. In this protocol, we developed a new system to identify target proteins in PC-3 cells of natural compound, Ganoderic acid DM (1). Ganoderic acid DM (1) is a naturally occurring triterpenoid of Ganoderma which exhibits distinct pharmacological effects. We used ganoderic acid DM-conjugated magnetic beads as a probe, and Tublin was identified as a ganoderic acid DM-binding protein using LC-MS/MS. Ganoderic acid DM should exert its cytotoxicity by binding with tubulin, and showed the microtubule-stabilizing activity comparable to the wellestablished antimitotic chemotherapeutic drug, paclitaxel. We also show that this technique is capable of detecting different target proteins of other compounds among cells. The whole protocol, starting from bead conjugation can be completed within 4 days.

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Anti‐Androgen Effects of Extracts and Compounds from Ganoderma lucidum

Cited by 21 publications

References 33 publications

Natural Ligands for Nuclear Receptors: Biology and Potential Therapeutic Applications

Natural Ligands for Nuclear Receptors: Biology and Potential Therapeutic Applications

Target proteins of ganoderic acid DM provides clues to various pharmacological mechanisms

A protocol for isolation of target proteins of natural compounds

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