title: 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: METHODS
  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.
  
  
  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.affiliation: Department of Bioengineering, Tatung University, Taipei, Taiwan.
authors.forename: Li-Chuan
authors.initials: LC
authors.lastname: Chung
authors.forename: Ke-Hung
authors.initials: KH
authors.lastname: Tsui
authors.forename: Tsui-Hsia
authors.initials: TH
authors.lastname: Feng
authors.forename: Shiow-Ling
authors.initials: SL
authors.lastname: Lee
authors.forename: Phei-Lang
authors.initials: PL
authors.lastname: Chang
authors.forename: Horng-Heng
authors.initials: HH
authors.lastname: Juang
mesh_terms: D000600:Amino Acids, Dicarboxylic / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D000975:Antioxidants / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D015687:Cell Hypoxia / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D017930:Genes, Reporter / Q000187:drug effects; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D007502:Iron Chelating Agents / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology; D008297:Male; D008898:Mimosine / Q000009:adverse effects / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D011393:Procollagen-Proline Dioxygenase / Q000037:antagonists & inhibitors; D017430:Prostate-Specific Antigen / Q000235:genetics / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D000600:Amino Acids, Dicarboxylic; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D004791:Enzyme Inhibitors; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D007502:Iron Chelating Agents; D009363:Neoplasm Proteins; D011994:Recombinant Proteins; D008898:Mimosine; D011393:Procollagen-Proline Dioxygenase; D017430:Prostate-Specific Antigen; D003474:Curcumin; C040947:oxalylglycine