title: Cancer cell-selective killing polymer/copper combination.
abstract: Chemotherapy has been adopted for cancer treatment for decades. However, its efficacy and safety are frequently compromised by the multidrug-resistance of cancer cells and the poor cancer cell selectivity of anticancer drugs. Hereby, we report a combination of a pyridine-2-thiol containing polymer and copper which can effectively kill a wide spectrum of cancer cells, including drug resistant cancer cells, while sparing normal cells. The polymer nanoparticle enters cells via an exofacial thiol facilitated route, and releases active pyridine-2-thiol with the help of intracellularly elevated glutathione (GSH). Due to their high GSH level, cancer cells are more vulnerable to the polymer/copper combination. In addition, RNA microarray analysis revealed that the treatment can reverse cancer cells' upregulated oncogenes (CIRBP and STMN1) and downregulated tumor suppressor genes (CDKN1C and GADD45B) to further enhance the selectivity for cancer cells.
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, SC 29208, USA. xup@sccp.sc.edu.
authors.forename: Huacheng
authors.initials: H
authors.lastname: He
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, SC 29208, USA. xup@sccp.sc.edu.
authors.forename: Diego
authors.initials: D
authors.lastname: Altomare
authors.affiliation: Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Ufuk
authors.initials: U
authors.lastname: Ozer
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, SC 29208, USA. xup@sccp.sc.edu.
authors.forename: Hanwen
authors.initials: H
authors.lastname: Xu
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, SC 29208, USA. xup@sccp.sc.edu.
authors.forename: Kim
authors.initials: K
authors.lastname: Creek
authors.affiliation: Department of Biological Sciences, University of South Carolina, Columbia, SC 29208, USA.
authors.forename: Hexin
authors.initials: H
authors.lastname: Chen
authors.affiliation: Department of Drug Discovery and Biomedical Sciences, University of South Carolina, Columbia, SC 29208, USA. xup@sccp.sc.edu.
authors.forename: Peisheng
authors.initials: P
authors.lastname: Xu
mesh_terms: D000943:Antigens, Differentiation / Q000737:chemistry* / Q000378:metabolism; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects*; D018432:Drug Resistance, Multiple / Q000187:drug effects*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005978:Glutathione / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D053758:Nanoparticles / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry* / Q000494:pharmacology*; D011108:Polymers / Q000494:pharmacology; D011725:Pyridines / Q000737:chemistry* / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry* / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects*; D000097642:GADD45 Proteins
chemical_list: D000943:Antigens, Differentiation; D000970:Antineoplastic Agents; D003300:Copper; D005978:Glutathione; D009942:Organometallic Compounds; D011108:Polymers; D011725:Pyridines; D016601:RNA-Binding Proteins; D013438:Sulfhydryl Compounds; C491390:CIRBP protein, human; C086470:GADD45B protein, human; D000097642:GADD45 Proteins; C000613706:pyridine-2-thiol