Hinokitiol, a metal chelator derived from natural plants, suppresses cell growth and disrupts androgen receptor signaling in prostate carcinoma cell lines.
Hinokitiol (beta-thujaplicin), a troplone-related compound found in the heartwood of cupressaceous plants, strongly inhibits the proliferation of a broad range of tumor cell lines. This is the first report to demonstrate that hinokitiol, a metal chelator derived from natural plants, suppresses cell growth and disrupts AR signaling in prostate carcinoma cell lines. Our present studies indicate that hinokitiol suppresses androgen/AR-mediated cell growth and androgen-stimulated DNA synthesis by [(3)H]thymidine incorporation in a dose- and time-dependent manner. Hinokitiol simultaneously suppresses the intracellular and secreted PSA levels, a marker for the progression of prostate cancer. Hinokitiol significantly represses the AR mRNA and protein expression in a dose- and time-dependent manner. Additionally, the ligand-binding assay shows that hinokitiol blocks binding of the synthetic androgen [(3)H]R1881 to AR in LNCaP cells. These findings collectively suggest that hinokitiol is potentially effective against prostate cancer in vitro, and thus it might become a novel chemopreventive or chemotherapeutic agent for prostate cancer.
Liu
Shicheng
S
Research Department, Saitama Daiichi Pharmaceutical Co., Ltd., 8-1, Minamisakae-cho, Kasukabe, Saitama 344-0057, Japan. riu@sdsk.co.jp
Yamauchi
Hitoshi
H
D000728:Androgens / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002614:Chelating Agents / Q000008:administration & dosage; D006801:Humans; D008297:Male; D008670:Metals / Q000008:administration & dosage; D039821:Monoterpenes / Q000008:administration & dosage*; D010936:Plant Extracts / Q000008:administration & dosage*; D017430:Prostate-Specific Antigen / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology*; D011944:Receptors, Androgen / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*; D014334:Tropolone / Q000008:administration & dosage / Q000031:analogs & derivatives*
D000728:Androgens; D002614:Chelating Agents; D008670:Metals; D039821:Monoterpenes; D010936:Plant Extracts; D011944:Receptors, Androgen; D014334:Tropolone; D017430:Prostate-Specific Antigen; C009479:beta-thujaplicin