title: Folate-functionalized human serum albumin carrier for anticancer copper(II) complexes derived from natural plumbagin.
abstract: The folate (FA)-functionalized human serum albumin (HSA) carrier (FA-HSA) is promising for improving the target and efficiency of anticancer drugs. To develop FA-HSA carrier for metal anticancer drugs, we investigated anticancer properties and mechanism of FA-HSA carrier for Cu(II) complexes derived from plumbagin. The fluorescence spectroscopy and molecular docking revealed that Cu(II) complexes bind to IIA subdomain of HSA. Compared with Cu(II) complex alone, FA-HSA-metallodrug complex enhances cytotoxicity to FA-positive cancer cells (HeLa) but do not raise cytotoxicity levels in normal cells in vitro through selectively accumulating in cancer cells to some extent; FA-HSA-metallodrug complex has a stronger capacity for cell cycle arrest in the G2/M phase of HeLa cells, and down-regulating the expression of cyclin-dependent kinase 1 (CDK1) and cyclin B1. Moreover, FA-HSA-metallodrug complex promotes HeLa cells apoptosis through intrinsic reactive oxygen species (ROS) mediated mitochondrial pathway, accompanied by the regulation of Bcl-2 family proteins.
authors.affiliation: Key Laboratory of Ecology of Rare and Endangered Species and Environmental Protection, Ministry of education of the People's Republic of China, Guangxi Normal University, Guilin, Guangxi, China; State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China. Guangxi Normal University, Guilin, Guangxi, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Gou
authors.affiliation: Key Laboratory of Ecology of Rare and Endangered Species and Environmental Protection, Ministry of education of the People's Republic of China, Guangxi Normal University, Guilin, Guangxi, China.
authors.forename: Zhan
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China. Guangxi Normal University, Guilin, Guangxi, China.
authors.forename: Jinxu
authors.initials: J
authors.lastname: Qi
authors.affiliation: Key Laboratory of Ecology of Rare and Endangered Species and Environmental Protection, Ministry of education of the People's Republic of China, Guangxi Normal University, Guilin, Guangxi, China.
authors.forename: Shichu
authors.initials: S
authors.lastname: Liang
authors.affiliation: Guangxi Universities Key Laboratory of Stem Cell and Pharmaceutical Biotechnology, Guangxi Normal University, Guilin, Guangxi, China.
authors.forename: Zuping
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Ecology of Rare and Endangered Species and Environmental Protection, Ministry of education of the People's Republic of China, Guangxi Normal University, Guilin, Guangxi, China; State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China. Guangxi Normal University, Guilin, Guangxi, China; Guangxi Universities Key Laboratory of Stem Cell and Pharmaceutical Biotechnology, Guangxi Normal University, Guilin, Guangxi, China. Electronic address: fyang@mailbox.gxnu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Yang
authors.affiliation: Key Laboratory of Ecology of Rare and Endangered Species and Environmental Protection, Ministry of education of the People's Republic of China, Guangxi Normal University, Guilin, Guangxi, China; State Key Laboratory Cultivation Base for the Chemistry and Molecular Engineering of Medicinal Resources, Ministry of Science and Technology of China. Guangxi Normal University, Guilin, Guangxi, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Liang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D016203:CDC2 Protein Kinase; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry*; D056744:Cyclin B1 / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000235:genetics; D045304:Cytochromes c / Q000235:genetics; D004337:Drug Carriers; D005492:Folic Acid / Q000031:analogs & derivatives* / Q000737:chemistry*; D006367:HeLa Cells; D006801:Humans; D061986:MCF-7 Cells; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D012709:Serum Albumin / Q000737:chemistry*; D051028:bcl-2-Associated X Protein / Q000235:genetics; D051025:bcl-Associated Death Protein / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; C494819:BAD protein, human; C494826:BAX protein, human; C534699:CCNB1 protein, human; D056831:Coordination Complexes; D056744:Cyclin B1; D004337:Drug Carriers; D009285:Naphthoquinones; D012709:Serum Albumin; D051028:bcl-2-Associated X Protein; D051025:bcl-Associated Death Protein; D003300:Copper; D045304:Cytochromes c; D005492:Folic Acid; D016203:CDC2 Protein Kinase; C528899:CDK1 protein, human; D018844:Cyclin-Dependent Kinases; C014758:plumbagin
keywords: Copper(II) complex; Drug carrier; Folate; Human serum albumin; Plumbagin