Abstract
Structurally related lanostane-type triterpenes, ganoderic acid A, F and H (GA-A, GA-F, GA-H), were identified in an oriental medicinal mushroom Ganoderma lucidum. In the present study we evaluated the effect of GA-A, GA-H and GA-F on highly invasive human breast cancer cells. We showed that GA-A and GA-H suppressed growth (cell proliferation and colony formation) and invasive behavior (adhesion, migration and invasion) of MDA-MB-231 cells. Our results suggest that GA-A and GA-H mediate their biological effects through the inhibition of transcription factors AP-1 and NF-kappaB, resulting in the down-regulation of expression of Cdk4 and the suppression of secretion of uPA, respectively. Furthermore, the activity of ganoderic acids is linked to the hydroxylation in the position 7 and 15 (GA-A) and 3 (GA-H) in their triterpene lanostane structure. In conclusion, hydroxylated triterpenes from G. lucidum could be promising natural agents for the therapy of invasive breast cancers.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use
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Breast Neoplasms / drug therapy
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Breast Neoplasms / metabolism*
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Breast Neoplasms / pathology
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Cell Line, Tumor / drug effects*
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Cyclin-Dependent Kinase 4 / metabolism
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Female
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Heptanoic Acids / chemistry
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Heptanoic Acids / pharmacology*
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Heptanoic Acids / therapeutic use
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Humans
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Lanosterol / analogs & derivatives*
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Lanosterol / chemistry
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Lanosterol / pharmacology
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Lanosterol / therapeutic use
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Molecular Structure
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NF-kappa B / metabolism*
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Reishi / chemistry
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Signal Transduction / physiology
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Transcription Factor AP-1 / metabolism*
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Urokinase-Type Plasminogen Activator / metabolism
Substances
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Antineoplastic Agents
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Heptanoic Acids
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NF-kappa B
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Transcription Factor AP-1
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ganoderic acid H
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Lanosterol
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ganoderic acid A
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ganoderic acid F
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Cyclin-Dependent Kinase 4
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Urokinase-Type Plasminogen Activator