title: The JAK2/STAT3 and mitochondrial pathways are essential for quercetin nanoliposome-induced C6 glioma cell death.
abstract: The formulation of quercetin nanoliposomes (QUE-NLs) has been shown to enhance QUE antitumor activity in C6 glioma cells. At high concentrations, QUE-NLs induce necrotic cell death. In this study, we probed the molecular mechanisms of QUE-NL-induced C6 glioma cell death and examined whether QUE-NL-induced programmed cell death involved Bcl-2 family and mitochondrial pathway through STAT3 signal transduction pathway. Downregulation of Bcl-2 and the overexpression of Bax by QUE-NL supported the involvement of Bcl-2 family proteins upstream of C6 glioma cell death. In addition, the activation of JAK2 and STAT3 were altered following exposure to QUE-NLs in C6 glioma cells, suggesting that QUE-NLs downregulated Bcl-2 mRNAs expression and enhanced the expression of mitochondrial mRNAs through STAT3-mediated signaling pathways either via direct or indirect mechanisms. There are several components such as ROS, mitochondrial, and Bcl-2 family shared by the necrotic and apoptotic pathways. Our studies indicate that the signaling cross point of the mitochondrial pathway and the JAK2/STAT3 signaling pathway in C6 glioma cell death is modulated by QUE-NLs. In conclusion, regulation of JAK2/STAT3 and ROS-mediated mitochondrial pathway agonists alone or in combination with treatment by QUE-NLs could be a more effective method of treating chemical-resistant glioma.
authors.affiliation: Department of Pharmacy, Taihe Hospital, Hubei University of Medicine, Shiyan City, Hubei Province, People's Republic of China.
authors.forename: G
authors.initials: G
authors.lastname: Wang
authors.forename: J J
authors.initials: JJ
authors.lastname: Wang
authors.forename: X L
authors.initials: XL
authors.lastname: Chen
authors.forename: S M
authors.initials: SM
authors.lastname: Du
authors.forename: D S
authors.initials: DS
authors.lastname: Li
authors.forename: Z J
authors.initials: ZJ
authors.lastname: Pei
authors.forename: H
authors.initials: H
authors.lastname: Lan
authors.forename: L B
authors.initials: LB
authors.lastname: Wu
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D048430:Cell Shape / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005910:Glioma; D006801:Humans; D053614:Janus Kinase 2 / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008081:Liposomes / Q000737:chemistry; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D053769:Nanocapsules / Q000737:chemistry; D009336:Necrosis; D010316:Particle Size; D011794:Quercetin / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D020032:Tyrphostins / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes; D053769:Nanocapsules; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D020032:Tyrphostins; C095512:alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; D011794:Quercetin; D007770:L-Lactate Dehydrogenase; C507924:JAK2 protein, human; D053614:Janus Kinase 2
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