Abstract
Scope:
Prostate-specific antigen (PSA) is a well-known marker for diagnosing and monitoring prostate cancer. Curcumin, a yellow curry pigment, has been reported to enhance androgen receptor (AR) degradation. We examined the effects of curcumin on increasing PSA expression by hypoxia and prolyl hydroxylase inhibitors, L-mimosine and dimethyloxalylglycine (DMOG), in human prostate carcinoma LNCaP cells.
Methods and results:
The 3H-thymidine incorporation assay revealed that either L-mimosine or DMOG treatments attenuated cell proliferation. Immunoblot and enzyme-linked immunosorbent assays (ELISA) indicated that both L-mimosine and DMOG have an effect similar to hypoxia, which stabilized hypoxia-inducible factor-1α (HIF-1α) and induced PSA gene expression. The results of the immunoblot and transient gene expression assays indicated that induction of the PSA expression by hypoxia is both HIF-1α- and AR-dependent. Immunoblot assays revealed that a curcumin treatment (10 μM) decreased the protein abundance of AR but did not significantly affect the protein levels of HIF-1α and vascular endothelial growth factor, which were induced by hypoxia. ELISA and transient gene expression assays indicated that curcumin blocked the activation of L-mimosine or DMOG treatment on PSA expression.
Conclusions:
These results indicate that curcumin blocked the enhanced effect of PSA expression by L-mimosine and DMOG that induce hypoxia condition.
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acids, Dicarboxylic / adverse effects
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Amino Acids, Dicarboxylic / antagonists & inhibitors
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Amino Acids, Dicarboxylic / pharmacology
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / antagonists & inhibitors
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents, Phytogenic / pharmacology*
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Antioxidants / pharmacology
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Carcinoma / drug therapy*
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Carcinoma / metabolism
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Cell Hypoxia / drug effects*
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Cell Line, Tumor
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Cell Proliferation / drug effects
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Curcumin / pharmacology*
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Enzyme Inhibitors / pharmacology
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Gene Expression Regulation, Neoplastic / drug effects*
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Genes, Reporter / drug effects
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / genetics
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Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
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Iron Chelating Agents / adverse effects
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Iron Chelating Agents / chemistry
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Iron Chelating Agents / pharmacology
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Male
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Mimosine / adverse effects
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Mimosine / antagonists & inhibitors
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Mimosine / pharmacology
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Neoplasm Proteins / antagonists & inhibitors
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Neoplasm Proteins / metabolism
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Procollagen-Proline Dioxygenase / antagonists & inhibitors
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Prostate-Specific Antigen / genetics
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Prostate-Specific Antigen / metabolism*
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Prostatic Neoplasms / drug therapy*
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Prostatic Neoplasms / metabolism
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Recombinant Proteins / metabolism
Substances
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Amino Acids, Dicarboxylic
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Antineoplastic Agents
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Antineoplastic Agents, Phytogenic
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Antioxidants
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Enzyme Inhibitors
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HIF1A protein, human
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Hypoxia-Inducible Factor 1, alpha Subunit
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Iron Chelating Agents
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Neoplasm Proteins
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Recombinant Proteins
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Mimosine
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Procollagen-Proline Dioxygenase
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Prostate-Specific Antigen
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Curcumin
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oxalylglycine