BTH-8, a novel poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor, causes DNA double-strand breaks and exhibits anticancer activities in vitro and in vivo
Copyright policy )BTH-8, a novel poly (ADP-ribose) polymerase-1 (PARP-1) inhibitor, causes DNA double-strand breaks and exhibits anticancer activities in vitro and in vivo
Poly (ADP-ribose) polymerase (PARP) is a family of enzymes that play an important role in DNA repair. We designed 2-(2,3,6-tribromo-4,5-dimethoxybenzylidene) hydrazinecarbothioamide (BTH-8) as a novel human PARP (PARP-1) inhibitor with anticancer activities in vitro and in vivo. With an IC50 value of 79.79 ± 2.16 nM, BTH-8 caused DNA double-strand breaks, increased the foci quantitation of γ-H2AX and inhibited poly(ADP-ribose) (PAR) formation. BTH-8 could bind to PARP-1 with the target affinity [KD (equilibrium dissociation constant) value] of 1.372 μM. BTH-8 can inhibit the proliferation of a variety of tumor cells, especially BRCA-deficient cells (HCC-1937 and Capan-1). Further investigation showed that BTH-8 effectively induced a significant amount of G2/M cell cycle arrest and cell apoptosis in HCC-1937 cells. BTH-8 also exhibited antitumor activity in vivo, which was achieved by the inhibition of PARP-1. In sum, our study indicates that BTH-8 might be a novel suitable PARP-1 inhibitor to treat human breast cancer.
- Shandong Women’s University China (People's Republic of)
- Chinese Academy of Sciences China (People's Republic of)
- State Key Laboratory of Microbial Technology China (People's Republic of)
- Qingdao University of Science and Technology China (People's Republic of)
- Qilu Hospital of Shandong University China (People's Republic of)
Models, Molecular, Binding Sites, Dose-Response Relationship, Drug, Molecular Structure, Molecular Conformation, Poly (ADP-Ribose) Polymerase-1, Antineoplastic Agents, Apoptosis, Poly(ADP-ribose) Polymerase Inhibitors, G2 Phase Cell Cycle Checkpoints, Disease Models, Animal, Mice, Cell Line, Tumor, Biomarkers, Tumor, Animals, Humans, DNA Breaks, Double-Stranded, Female, Cell Proliferation, Protein Binding
Models, Molecular, Binding Sites, Dose-Response Relationship, Drug, Molecular Structure, Molecular Conformation, Poly (ADP-Ribose) Polymerase-1, Antineoplastic Agents, Apoptosis, Poly(ADP-ribose) Polymerase Inhibitors, G2 Phase Cell Cycle Checkpoints, Disease Models, Animal, Mice, Cell Line, Tumor, Biomarkers, Tumor, Animals, Humans, DNA Breaks, Double-Stranded, Female, Cell Proliferation, Protein Binding
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