title: Targeting of Topoisomerase I for Prognoses and Therapeutics of Camptothecin-Resistant Ovarian Cancer.
abstract: DNA topoisomerase I (TOP1) levels of several human neoplasms are higher than those of normal tissues. TOP1 inhibitors are widely used in treating conventional therapy-resistant ovarian cancers. However, patients may develop resistance to TOP1 inhibitors, hampering chemotherapy success. In this study, we examined the mechanisms associated with the development of camptothecin (CPT) resistance in ovarian cancers and identified evodiamine (EVO), a natural product with TOP1 inhibiting activity that overcomes the resistance. The correlations among TOP1 levels, cancer staging, and overall survival (OS) were analyzed. The effect of EVO on CPT-resistant ovarian cancer was evaluated in vitro and in vivo. TOP1 was associated with poor prognosis in ovarian cancers (p = 0.024). EVO induced apoptosis that was detected using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The tumor size decreased significantly in the EVO treatment group compared with the control group (p < 0.01) in a xenograft mouse model. Effects of drugs targeting TOP1 for prognosis and therapy in CPT-resistant ovarian cancer are anticipated. EVO with TOP1 can be developed as an antiproliferative agent for overcoming CPT resistance in ovarian cancers.
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yu-Chieh
authors.initials: YC
authors.lastname: Lee
authors.affiliation: Department of Pathology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan.
authors.forename: Chii-Hong
authors.initials: CH
authors.lastname: Lee
authors.affiliation: Department of Biochemistry, School of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Hsiang-Ping
authors.initials: HP
authors.lastname: Tsai
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Herng-Wei
authors.initials: HW
authors.lastname: An
authors.affiliation: Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chi-Ming
authors.initials: CM
authors.lastname: Lee
authors.affiliation: Center for Stem Cells and Translational Cancer Research, Chang Gung Memorial Hospital, Gueishan, Taoyuan County, Taiwan.
authors.forename: Jen-Chine
authors.initials: JC
authors.lastname: Wu
authors.affiliation: School of Pharmacy, China Medical University, Taichung, Taiwan.
authors.forename: Chien-Shu
authors.initials: CS
authors.lastname: Chen
authors.affiliation: Department of Food and Beverage Management, Taipei College of Maritime Technology, Taipei, Taiwan.
authors.forename: Shih-Hao
authors.initials: SH
authors.lastname: Huang
authors.affiliation: Department of Biochemistry, School of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Jaulang
authors.initials: J
authors.lastname: Hwang
authors.affiliation: Department of Biochemistry, School of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Kur-Ta
authors.initials: KT
authors.lastname: Cheng
authors.affiliation: Department of Pathology, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan.
authors.forename: Phui-Ly
authors.initials: PL
authors.lastname: Leiw
authors.affiliation: Department of Pathology, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Pathology, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Chi-Long
authors.initials: CL
authors.lastname: Chen
authors.affiliation: Department of Biochemistry, School of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Chun-Mao
authors.initials: CM
authors.lastname: Lin
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis; D002166:Camptothecin / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D006801:Humans; D026121:Indole Alkaloids / Q000008:administration & dosage* / Q000494:pharmacology; D051379:Mice; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D016896:Treatment Outcome; D023041:Xenograft Model Antitumor Assays
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D026121:Indole Alkaloids; C539353:evodamine; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D002166:Camptothecin