title: Influence of hexabromocyclododecane and 4-nonylphenol on the regulation of cell growth, apoptosis and migration in prostatic cancer cells.
abstract: The aim of the present study was to determine whether hexabromocyclododecane (HBCD) or 4-nonylphenol (NP) may induce prostatic cancer progression in LNCaP cells. Androgenic effects of HBCD and NP were examined in LNCaP prostate cancer cells expressing androgen receptors (ARs). HBCD and NP increased LNCaP cell viability similar to dihydrotestosterone (DHT) by MTT assay. This phenomenon was reversed by treatment with Casodex, an AR antagonist, suggesting that they act as xenoandrogens via AR signaling pathway. In cell migration assay, HBCD and NP also enhanced LNCaP cell migration similar to DHT. To elucidate underlying mechanisms of their actions on LNCaP, transcriptional levels of cell cycle- and apoptosis-related markers, including cyclin D1, cyclin E, p27, bcl-2, and bax, were determined by reverse transcription (RT)-PCR. An increase in expression cyclin D1 and cyclin E and reduction in p27 and bax mRNA levels were observed by their treatments. Western blot assay showed their alterations in translational levels of cyclin D1, cyclin E, p21, bax, and cathepsin D. Expressions of genes related to a G1/S transition of cell cycle and cathepsin D were elevated, while expression of p21 and bax was decreased. Taken together, these results indicate that HBCD and NP may enhance progression of prostate cancer by modulating growth and migration of LNCaP prostate cells by acting on cell cycle, apoptosis, and metastasis.
authors.affiliation: Laboratory of Biochemistry and Immunology, College of Medicine, Chungbuk National University, Cheongju, Chungbuk, 361-763, Republic of Korea.
authors.forename: Seung-Hee
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, 30 Yeongudanji-ro, Ochang-eup, Cheongwon-gun, Chungbuk, Republic of Korea.
authors.forename: Ki-Hoan
authors.initials: KH
authors.lastname: Nam
authors.affiliation: Laboratory of Biochemistry and Immunology, College of Medicine, Chungbuk National University, Cheongju, Chungbuk, 361-763, Republic of Korea. Electronic address: hka9400@naver.com.
authors.forename: Kyung-A
authors.initials: KA
authors.lastname: Hwang
authors.affiliation: Laboratory of Biochemistry and Immunology, College of Medicine, Chungbuk National University, Cheongju, Chungbuk, 361-763, Republic of Korea. Electronic address: kchoi@cbu.ac.kr.
authors.forename: Kyung-Chul
authors.initials: KC
authors.lastname: Choi
mesh_terms: D000728:Androgens / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002402:Cathepsin D / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D019927:Cyclin E / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D052244:Endocrine Disruptors / Q000633:toxicity*; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000633:toxicity*; D008297:Male; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D010636:Phenols / Q000633:toxicity*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D000728:Androgens; C494826:BAX protein, human; C530104:CCND1 protein, human; C475820:CCNE1 protein, human; C493956:CDKN1A protein, human; D019927:Cyclin E; D050759:Cyclin-Dependent Kinase Inhibitor p21; D052244:Endocrine Disruptors; D006842:Hydrocarbons, Brominated; D015513:Oncogene Proteins; D010636:Phenols; D051028:bcl-2-Associated X Protein; D019938:Cyclin D1; C089796:hexabromocyclododecane; D002402:Cathepsin D; C041594:4-nonylphenol
keywords: 4-Nonylphenol; Apoptosis; Cell proliferation; Hexabromocyclododecane; Migration; Prostate cancer