Curcumin provides potential protection against the activation of hypoxia and prolyl 4-hydroxylase inhibitors on prostate-specific antigen expression in human prostate carcinoma cells.

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.

• Authors: Li-Chuan Chung, Ke-Hung Tsui, Tsui-Hsia Feng, Shiow-Ling Lee, Phei-Lang Chang, Horng-Heng Juang
• Journal: Molecular nutrition & food research (Mol Nutr Food Res) Vol. 55 Issue 11 Pg. 1666-76 (Nov 2011) ISSN: 1613-4133 [Electronic] Germany
• PMID: 21936051 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Chemical References

• Amino Acids, Dicarboxylic
• Antineoplastic Agents
• Antineoplastic Agents, Phytogenic
• Antioxidants
• Enzyme Inhibitors
• HIF1A protein, human
• Hypoxia-Inducible Factor 1, alpha Subunit
• Iron Chelating Agents
• Neoplasm Proteins
• Recombinant Proteins
• Mimosine
• Procollagen-Proline Dioxygenase
• Prostate-Specific Antigen
• Curcumin
• oxalylglycine

Topics

• Amino Acids, Dicarboxylic (adverse effects, antagonists & inhibitors, pharmacology)
• Antineoplastic Agents (adverse effects, antagonists & inhibitors, pharmacology)
• Antineoplastic Agents, Phytogenic (pharmacology)
• Antioxidants (pharmacology)
• Carcinoma (drug therapy, metabolism)
• Cell Hypoxia (drug effects)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Curcumin (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Gene Expression Regulation, Neoplastic (drug effects)
• Genes, Reporter (drug effects)
• Humans
• Hypoxia-Inducible Factor 1, alpha Subunit (genetics, metabolism)
• Iron Chelating Agents (adverse effects, chemistry, pharmacology)
• Male
• Mimosine (adverse effects, antagonists & inhibitors, pharmacology)
• Neoplasm Proteins (antagonists & inhibitors, metabolism)
• Procollagen-Proline Dioxygenase (antagonists & inhibitors)
• Prostate-Specific Antigen (genetics, metabolism)
• Prostatic Neoplasms (drug therapy, metabolism)
• Recombinant Proteins (metabolism)