title: Tebufenozide induces G1/S cell cycle arrest and apoptosis in human cells.
abstract: Tebufenozide is a non-steroidal insect growth regulator and is extensively used to control pests, although it is considered to be safe for mammals and environmentally friendly. However, previous studies have found that tebufenozide is cytotoxic to man, although the exact mechanism remains elusive. This study will investigate the apoptotic molecular mechanisms which result from tebufenozide-induced DNA damage in HeLa cells. Our results demonstrate that tebufenozide could trigger arrest in G1/S phase related to a downregulation of cyclin E and cyclin-dependent kinase (CDK) 2 protein. In addition, Western blotting showed apoptosis was associated with the upregulation of p53, Bax and cleaved-PARP, as well as downregulation of Bcl-2 and PARP. Tebufenozide also regulated changes in mitochondrial permeability and reduced mitochondrial number and intracellular ATP production. Briefly, these results suggest that tebufenozide- induces cell cycle arrest and apoptosis through activating p53 protein in a Bax- and Bcl-2-triggered mitochondrial pathway. This work provides some scientific context for the safe use of tebufenozide in agriculture.
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Wenping
authors.initials: W
authors.lastname: Xu
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Mingjun
authors.initials: M
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Yun
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
authors.forename: Haijing
authors.initials: H
authors.lastname: Cao
authors.affiliation: Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China. Electronic address: taolm@ecust.edu.cn.
authors.forename: Liming
authors.initials: L
authors.lastname: Tao
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D004249:DNA Damage; D006367:HeLa Cells; D006801:Humans; D006834:Hydrazines / Q000633:toxicity*; D007306:Insecticides / Q000633:toxicity*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D006834:Hydrazines; D007306:Insecticides; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; C082026:tebufenozide
keywords: Apoptosis; Cell cycle arrest; Cytotoxic effects; DNA damage; Pesticide; Tebufenozide