title: The pterocarpanquinone LQB-118 inhibits tumor cell proliferation by downregulation of c-Myc and cyclins D1 and B1 mRNA and upregulation of p21 cell cycle inhibitor expression.
abstract: The incidence of cancer grows annually worldwide and in Brazil it is the second cause of death. The search for anti-cancer drugs has then become urgent. It depends on the studies of natural and chemical synthesis products. The antitumor action of LQB-118, a pterocarpanquinone structurally related to lapachol, has been demonstrated to induce mechanisms linked to leukemia cell apoptosis. This work investigated some mechanisms of the in vitro antitumor action of LQB-118 on prostate cancer cells. LQB-118 reduced the expression of the c-Myc transcription factor, downregulated the cyclin D1 and cyclin B1 mRNA levels and upregulated the p21 cell cycle inhibitor. These effects resulted in cell cycle arrest in the S and G2/M phases and inhibition of tumor cell proliferation. LQB-118 also induced programmed cell death of the prostate cancer cells, as evidenced by internucleosomal DNA fragmentation and annexin-V positive cells. Except the cell cycle arrest in the S phase and enhanced c-Myc expression, all the mechanisms observed here for the in vitro antitumor action of LQB-118 were also found for Paclitaxel, a traditional antineoplastic drug. These findings suggest new molecular mechanisms for the LQB-118 in vitro antitumor action.
authors.affiliation: Department of Biochemistry, Biomedical Center, Rio de Janeiro State University, Boulevard 28 de Setembro, 87, fundos, 4° andar, PAPC, Rio de Janeiro, RJ CEP 20551-030, Brazil.
authors.forename: Thiago
authors.initials: T
authors.lastname: Martino
authors.affiliation: Department of Biochemistry, Biomedical Center, Rio de Janeiro State University, Boulevard 28 de Setembro, 87, fundos, 4° andar, PAPC, Rio de Janeiro, RJ CEP 20551-030, Brazil.
authors.forename: Fernanda C J
authors.initials: FC
authors.lastname: Magalhães
authors.affiliation: Department of Biochemistry, Biomedical Center, Rio de Janeiro State University, Boulevard 28 de Setembro, 87, fundos, 4° andar, PAPC, Rio de Janeiro, RJ CEP 20551-030, Brazil.
authors.forename: Graça A
authors.initials: GA
authors.lastname: Justo
authors.affiliation: Department of Biochemistry, Biomedical Center, Rio de Janeiro State University, Boulevard 28 de Setembro, 87, fundos, 4° andar, PAPC, Rio de Janeiro, RJ CEP 20551-030, Brazil.
authors.forename: Marsen G P
authors.initials: MG
authors.lastname: Coelho
authors.affiliation: Laboratory of Bioorganic Chemistry, Research Nucleous of Natural Products, Rio de Janeiro Federal University, Rio de Janeiro, Brazil.
authors.forename: Chaquip D
authors.initials: CD
authors.lastname: Netto
authors.affiliation: Laboratory of Bioorganic Chemistry, Research Nucleous of Natural Products, Rio de Janeiro Federal University, Rio de Janeiro, Brazil.
authors.forename: Paulo R R
authors.initials: PR
authors.lastname: Costa
authors.affiliation: Department of Biochemistry, Biomedical Center, Rio de Janeiro State University, Boulevard 28 de Setembro, 87, fundos, 4° andar, PAPC, Rio de Janeiro, RJ CEP 20551-030, Brazil. Electronic address: kasabino2000@yahoo.com.br.
authors.forename: Kátia C C
authors.initials: KC
authors.lastname: Sabino
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D019938:Cyclin D1 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008297:Male; D009285:Naphthoquinones / Q000494:pharmacology*; D011471:Prostatic Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D036343:Pterocarpans / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
chemical_list: D050759:Cyclin-Dependent Kinase Inhibitor p21; C569361:LQB 118; D009285:Naphthoquinones; D016271:Proto-Oncogene Proteins c-myc; D036343:Pterocarpans; D012333:RNA, Messenger; D019938:Cyclin D1
keywords: Apoptosis; Cell cycle; Cyclins; LQB-118; PC3 cells; c-Myc