title: Targeting thioredoxin reductase by plumbagin contributes to inducing apoptosis of HL-60 cells.
abstract: Plumbagin (PLB), a natural naphthoquinone from the traditional folk medicines Plumbago zeylanica, Dionaea muscipula, or Nepenthes gracilis, has been documented possessing a wide variety of pharmacological activities. Although PLB demonstrates anticancer activity in multiple types of malignant cells, the cellular targets of PLB have not been well defined and remained only partially understood. We reported here that PLB selectively inhibits TrxR and elicits reactive oxygen species in human promyelocytic leukemia HL-60 cells, which leads to elevation of GSSG/GSH ratio and decrease of cellular thiol pool. As a consequence, PLB disturbs the cellular redox homeostasis, induces oxidative stress-mediated apoptosis and eventually selectively kills HL-60 cells. Inhibition of TrxR by PLB thus discloses an unprecedented mechanism underlying the anticancer efficacy of PLB, and sheds light in considering the usage of PLB as a promising cancer therapeutic agent.
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, China; School of Pharmacy, Lanzhou University, Lanzhou, Gansu 730000, China.
authors.forename: Junmin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, China.
authors.forename: Shoujiao
authors.initials: S
authors.lastname: Peng
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, China.
authors.forename: Xinming
authors.initials: X
authors.lastname: Li
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, China.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Liu
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Han
authors.affiliation: State Key Laboratory of Applied Organic Chemistry, College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou, Gansu 730000, China. Electronic address: fangjg@lzu.edu.cn.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Fang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival; D057809:HEK293 Cells; D018922:HL-60 Cells; D006367:HeLa Cells; D056945:Hep G2 Cells; D006801:Humans; D009285:Naphthoquinones / Q000737:chemistry*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011485:Protein Binding; D017382:Reactive Oxygen Species / Q000378:metabolism; D013880:Thioredoxin-Disulfide Reductase / Q000378:metabolism*
chemical_list: D000970:Antineoplastic Agents; D009285:Naphthoquinones; D017382:Reactive Oxygen Species; D013880:Thioredoxin-Disulfide Reductase; C505407:CASP3 protein, human; D053148:Caspase 3; C014758:plumbagin
keywords: Anticancer; Apoptosis; Oxidative stress; Plumbagin; Thioredoxin reductase