title: Recombinant Lz-8 from Ganoderma lucidum induces endoplasmic reticulum             stress-mediated autophagic cell death in SGC-7901 human gastric cancer cells.
abstract: In Asia, the mushroom of the fungus Ganoderma lucidum has been widely used             as a traditional medicine for the past two millennia. The aim of this study was             to investigate the anticancer activity of recombinant Lz-8 (rLz-8), a protein             belonging to a family of fungal immunomodulatory proteins. We report that rLz-8             induces endoplasmic reticulum (ER) stress-mediated autophagic cell death in the             human gastric cancer cell line SGC-7901. Our results show that rLz-8 induces autophagic             cell death by aggregating in the ER, triggering ER stress and the ATF4-CHOP pathway.             A foreign protein, in the ER rLz-8 causes the activation of the ubiquitine/proteasome             ER-associated degradation (ERAD) system. The autophagic arm of this system is             then overstimulated by an excessive abundance of rLz-8 and causes the cell's death             through an over-autophagic response. We also found that caspase inhibitors do             not prevent rLz-8-induced cell death, and therefore the autophagic response induced             by rLz-8 is independent of caspase activation.
authors.affiliation: Institute of Frontier Medical Science of Jilin University, Changchun 130021, PR China.
authors.forename: Chongyang
authors.initials: C
authors.lastname: Liang
authors.forename: Hongrui
authors.initials: H
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Zhou
authors.forename: Shuqin
authors.initials: S
authors.lastname: Zhang
authors.forename: Zhiyi
authors.initials: Z
authors.lastname: Liu
authors.forename: Qiuli
authors.initials: Q
authors.lastname: Zhou
authors.forename: Fei
authors.initials: F
authors.lastname: Sun
mesh_terms: D051701:Activating Transcription Factor 4 / Q000235:genetics / Q000378:metabolism; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001343:Autophagy / Q000187:drug effects*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004721:Endoplasmic Reticulum / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects*; D060746:Endoplasmic Reticulum-Associated Degradation / Q000187:drug effects; D005656:Fungal Proteins / Q000096:biosynthesis / Q000235:genetics / Q000494:pharmacology*; D006801:Humans; D034622:RNA Interference; D011994:Recombinant Proteins / Q000494:pharmacology; D020940:Reishi / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D013997:Time Factors; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: C497109:ATF4 protein, human; D000970:Antineoplastic Agents; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C497249:DDIT3 protein, human; D005656:Fungal Proteins; D011994:Recombinant Proteins; C061148:LZ-8 protein, Ganoderma lucidum; D051701:Activating Transcription Factor 4; D051742:Transcription Factor CHOP; D020169:Caspases