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

Mol Nutr Food Res. 2011 Nov;55(11):1666-76. doi: 10.1002/mnfr.201100328. Epub 2011 Sep 21.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids, Dicarboxylic / adverse effects
  • Amino Acids, Dicarboxylic / antagonists & inhibitors
  • Amino Acids, Dicarboxylic / pharmacology
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / antagonists & inhibitors
  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Antioxidants / pharmacology
  • Carcinoma / drug therapy*
  • Carcinoma / 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
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
  • Iron Chelating Agents / adverse effects
  • Iron Chelating Agents / chemistry
  • Iron Chelating Agents / pharmacology
  • Male
  • Mimosine / adverse effects
  • Mimosine / antagonists & inhibitors
  • Mimosine / pharmacology
  • Neoplasm Proteins / antagonists & inhibitors
  • Neoplasm Proteins / metabolism
  • Procollagen-Proline Dioxygenase / antagonists & inhibitors
  • Prostate-Specific Antigen / genetics
  • Prostate-Specific Antigen / metabolism*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Recombinant Proteins / metabolism

Substances

  • 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