title: Antiproliferative effect of a synthetic aptamer mimicking androgen response elements in the LNCaP cell line.
abstract: Prostate cancer usually develops to a hormone-refractory state that is irresponsive to conventional therapeutic approaches. Therefore, new methods for treating aggressive prostate cancer are under development. Because of the importance of androgen receptors (ARs) in the development of the hormone-refractory state and AR mechanism of action, this study was designed. A single-stranded DNA as an aptamer was designed that could mimic the hormone response element (HRE). The LNCaP cells as an AR-rich model were divided into three sets of triplicate groups: the test group was transfected with Aptamer Mimicking HRE (AMH), Mock received only transfection reagents (mock) and a negative control. All three sets received 0, 10 and 100 nM of dehydroepiandrosterone (DHEA) separately. Data analysis showed hormone dependency of LNCaP cells in the negative control group upon treatment with 10 and 100 nM DHEA (compared with cells left untreated (P=0.001)). Transfection of AMH resulted in significant reduction of proliferation in the test group when compared with the negative control group with 10 (P=0.001) or 100 nM DHEA (P=0.02). AMH can form a hairpin structure at 37 °C and mimic the genomic HRE. Hence, it is capable of effectively competing with genomic HRE and interrupting the androgen signaling pathway in a prostate cancer cell line (LNCaP).
authors.affiliation: Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: S
authors.initials: S
authors.lastname: Kouhpayeh
authors.affiliation: Department of Biology, International Pardis, University of Guilan, Rasht, Iran.
authors.forename: A R
authors.initials: AR
authors.lastname: Einizadeh
authors.affiliation: Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: Z
authors.initials: Z
authors.lastname: Hejazi
authors.affiliation: Isfahan Cardiovascular Research Center, Cardiovascular Research Institute, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Boshtam
authors.affiliation: Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: L
authors.initials: L
authors.lastname: Shariati
authors.affiliation: Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Mirian
authors.affiliation: Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: L
authors.initials: L
authors.lastname: Darzi
authors.affiliation: Department of Biology, International Pardis, University of Guilan, Rasht, Iran.
authors.forename: M
authors.initials: M
authors.lastname: Sojoudi
authors.affiliation: Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.|Isfahan Pharmaceutical Science Research Center, School of Pharmacy and Pharmaceutical Science, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: H
authors.initials: H
authors.lastname: Khanahmad
authors.affiliation: Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran.
authors.forename: A
authors.initials: A
authors.lastname: Rezaei
mesh_terms: D000728:Androgens / Q000378:metabolism*; D052157:Aptamers, Nucleotide / Q000235:genetics*; D001483:Base Sequence; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D002470:Cell Survival / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics; D011944:Receptors, Androgen / Q000235:genetics*; D020218:Response Elements; D014162:Transfection
chemical_list: D000728:Androgens; D052157:Aptamers, Nucleotide; D012333:RNA, Messenger; D011944:Receptors, Androgen