title: Diosgenin induces apoptosis in IGF-1-stimulated human thyrocytes through two caspase-dependent pathways.
abstract: Insulin-like growth factor-1 (IGF-1) is a growth factor of the thyroid that has been shown in our previous study to possess proliferative and antiapoptotic effects in FRTL-5 cell lines through the upregulation of cyclin D and Fas-associated death domain-like interleukin-1-converting enzyme (FLICE)-inhibitory protein (FLIP). Diosgenin, a natural steroid sapogenin from plants, has been shown to induce apoptosis in many cell lines, with the exception of thyroid cells. In this report, we investigated the apoptotic effect and mechanism of diosgenin in IGF-1-stimulated primary human thyrocytes. Primary human thyrocytes were preincubated with or without IGF-1 for 24h and subsequently exposed to varying concentrations of diosgenin for different times. We found that diosgenin induced apoptosis in human thyrocytes pretreated with IGF-1 in a dose-dependent manner through the activation of caspase cascades. Moreover, diosgenin inhibited FLIP and activated caspase-8 in the FAS-related apoptotic pathway. Diosgenin increased the production of ROS, regulated the balance of Bax and Bcl-2 and cleaved caspase-9 in the mitochondrial apoptotic pathway. These results indicate that diosgenin induces apoptosis in IGF-1-stimulated primary human thyrocytes through two caspase-dependent pathways.
authors.affiliation: Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
authors.forename: Shumin
authors.initials: S
authors.lastname: Mu
authors.forename: Xingsong
authors.initials: X
authors.lastname: Tian
authors.forename: Yongwei
authors.initials: Y
authors.lastname: Ruan
authors.forename: Yuantao
authors.initials: Y
authors.lastname: Liu
authors.forename: Dezhi
authors.initials: D
authors.lastname: Bian
authors.forename: Chunyan
authors.initials: C
authors.lastname: Ma
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Yu
authors.forename: Mei
authors.initials: M
authors.lastname: Feng
authors.forename: Furong
authors.initials: F
authors.lastname: Wang
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.forename: Jia-Jun
authors.initials: JJ
authors.lastname: Zhao
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000737:chemistry; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein / Q000096:biosynthesis; D020169:Caspases / Q000096:biosynthesis*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004144:Diosgenin / Q000494:pharmacology*; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D013194:Staining and Labeling; D013961:Thyroid Gland / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D001562:Benzimidazoles; D053446:CASP8 and FADD-Like Apoptosis Regulating Protein; D005456:Fluorescent Dyes; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D007334:Insulin-Like Growth Factor I; D020169:Caspases; D004144:Diosgenin; C017807:bisbenzimide ethoxide trihydrochloride