title: Melittin protein inhibits the proliferation of MG63 cells by activating inositol-requiring protein-1α and X-box binding protein 1-mediated apoptosis.
abstract: The aim of the present study was to explore the pro-apoptotic effect and specific mechanism of action of melittin (MEL) in humans. The effects of MEL on apoptosis in osteosarcoma and fetal osteoblast cells were investigated, and the mechanism that induced MG63 cell growth was also explored. The effects of MEL on cell proliferation were detected by a 2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide analysis. Apoptosis was detected by flow cytometric analysis. MEL protein, inositol-requiring protein-1 (IRE-α), phosphorylated-protein kinase R-like endoplasmic reticulum (ER) kinase, spliced X-box-1 (XBP1), eukaryotic translation initiation factor-2α, cleaved activating transcription factor-6, caspase-12 and C/EBP homology protein (CHOP) were detected in three groups and two cell lines by western blot analysis. The results indicated that the expression or incubation of MEL in the MG63 cells triggered apoptosis and the inhibition of proliferation. One protein from the ER stress unfolded protein response pathway, IRE-α, was involved in the MEL-induced apoptosis in MG63 cells. Furthermore, spliced XBP1 protein was significantly increased in the MEL peptide incubated and MEL expressing groups of MG63 cells. Furthermore, CHOP protein expression was activated in MG63 cells following being incubated with or expressing MEL. In conclusion, MEL serves as an effective factor that inhibits the proliferation of MG63 cells via activating the ER stress-mediated apoptosis pathway. This activation is triggered by the IRE-α pathway mediated by inducing CHOP protein expression.
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fan
authors.affiliation: Department of Orthopedics, People's Hospital of Jimo, Qingdao, Shandong 266200, P.R. China.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Orthopedics, People's Hospital of Jimo, Qingdao, Shandong 266200, P.R. China.
authors.forename: Haidong
authors.initials: H
authors.lastname: Pang
authors.affiliation: Department of Orthopedics, People's Hospital of Jimo, Qingdao, Shandong 266200, P.R. China.
authors.forename: Jintang
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, People's Hospital of Jimo, Qingdao, Shandong 266200, P.R. China.
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Qilu Hospital of Shandong University, Jinan, Shandong 250012, P.R. China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Li
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D004722:Endoribonucleases / Q000378:metabolism*; D006801:Humans; D008555:Melitten / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000071701:Regulatory Factor X Transcription Factors; D051742:Transcription Factor CHOP / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D056811:Unfolded Protein Response / Q000187:drug effects; D000071717:X-Box Binding Protein 1
chemical_list: D004268:DNA-Binding Proteins; D000071701:Regulatory Factor X Transcription Factors; D014157:Transcription Factors; D000071717:X-Box Binding Protein 1; C000605543:XBP1 protein, human; D051742:Transcription Factor CHOP; D008555:Melitten; C528229:ERN1 protein, human; D017346:Protein Serine-Threonine Kinases; D004722:Endoribonucleases