title: Oroxylin A inhibits ATRA-induced IL-6 expression involved in retinoic acid syndrome by down-regulating CHOP.
abstract: Production of IL-6 constituted the major cause of death in the ATRA trial called retinoic acid syndrome (RAS). LAP and LIP are active and inactive isoforms of C/EBPβ, respectively. Inactive LIP dimerized with LAP to eliminate its activity. Following treatment with ATRA, CHOP expression was increased and dimerized with LIP more preferentially than LAP to rescue function of LAP. Oroxylin A has been reported to activate CHOP, a key mediator of unfolded protein response (UPR) pathway, and resulted in apoptosis. Interestingly, we found that low concentration of oroxylin A (≦ 40 μM) showed no apoptosis effect on NB4 and HL-60 cells and decreased the CHOP protein level via promoting its degradation. MG132 was utilized to conform the effect of oroxylin A on degrading CHOP. Our results showed that oroxylin A decreased the level of IL-6 secretion of NB4 cells with or without ATRA treatment while the effect was eliminated by C/EBPβ siRNA. We conclude that oroxylin A possessed abilities of inhibiting the ATRA-induced IL-6 production via modulation of LAP/LIP/CHOP in leukemia cell lines, which could providing a therapeutic strategy for RAS.
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors.forename: Hui
authors.initials: H
authors.lastname: Hui
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors.forename: Hao
authors.initials: H
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors.forename: Qinsheng
authors.initials: Q
authors.lastname: Dai
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors.forename: Jing
authors.initials: J
authors.lastname: Yao
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China.
authors.forename: Kai
authors.initials: K
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China. Electronic address: anticancer_drug@163.com.
authors.forename: Qinglong
authors.initials: Q
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, People's Republic of China. Electronic address: luna555@163.com.
authors.forename: Na
authors.initials: N
authors.lastname: Lu
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects*; D005419:Flavonoids / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism*; D020014:K562 Cells; D007976:Leupeptins / Q000494:pharmacology; D034622:RNA Interference; D013577:Syndrome; D051742:Transcription Factor CHOP / Q000235:genetics / Q000378:metabolism*; D014212:Tretinoin / Q000009:adverse effects / Q000494:pharmacology*; D020298:U937 Cells
chemical_list: D000970:Antineoplastic Agents; D022782:CCAAT-Enhancer-Binding Protein-beta; C497249:DDIT3 protein, human; D005419:Flavonoids; D015850:Interleukin-6; D007976:Leupeptins; D051742:Transcription Factor CHOP; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one; D014212:Tretinoin; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde
keywords: CHOP; IL-6; Oroxylin A; Retinoic acid syndrome