title: Shikonin inhibits the growth of human prostate cancer cells via modulation of the androgen receptor.
abstract: Shikonin, a natural naphthoquinone isolated from the traditional Chinese medicine Zi Cao (gromwell), has been shown to possess tumor cell killing activity. The human androgen receptor (AR) is a nuclear transcription factor that serves as a major therapeutic target for prostate cancer. However, AR regulation by shikonin has not been reported. We investigated the effects of shikonin on the growth of prostate cancer cells. We observed that shikonin decreased the expression of AR at both the mRNA and the protein levels in LNCaP and 22RV1 human prostate cancer cells. The results from a luciferase assay showed that shikonin decreased the transcriptional activity of AR. Moreover, shikonin treatment inhibited AR target gene expression, PSA and growth inhibition of prostate cancer cells. In conclusion, the present study shows for the first time that shikonin treatment causes transcriptional repression of AR and inhibition of its nuclear localization in human prostate cancer cells. We propose that shikonin, an anticancer drug extracted from natural sources, induces inhibition of cell growth through modulation of AR in androgen-responsive prostate cancer cells and is a candidate for use in cancer chemotherapy for human prostate cancer.
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Soon Young
authors.initials: SY
authors.lastname: Jang
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Eun Hyang
authors.initials: EH
authors.lastname: Jang
authors.affiliation: Department of Life and Nanopharmaceutical Science, Kyung Hee University, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Seo Young
authors.initials: SY
authors.lastname: Jeong
authors.affiliation: Department of Pharmaceutical Science, College of Pharmacy, Kyung Hee University, Dongdaemun-gu, Seoul 130-701, Republic of Korea.
authors.forename: Jong-Ho
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D009285:Naphthoquinones / Q000494:pharmacology*; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000473:pathology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: C410798:AR protein, human; D000970:Antineoplastic Agents; D009285:Naphthoquinones; D011944:Receptors, Androgen; C016101:shikonin; D017430:Prostate-Specific Antigen