6 results on '"Jin-Jian Lu"'
Search Results
2. Myricetin inhibits interferon-γ-induced PD-L1 and IDO1 expression in lung cancer cells
- Author
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Yu-Chi Chen, Xin-Ling He, Lu Qi, Wei Shi, Luo-Wei Yuan, Mu-Yang Huang, Yu-Lian Xu, Xiuping Chen, Lei Gu, Le-Le Zhang, and Jin-Jian Lu
- Subjects
Flavonoids ,Pharmacology ,Lung Neoplasms ,Dose-Response Relationship, Drug ,HCT116 Cells ,Biochemistry ,B7-H1 Antigen ,Coculture Techniques ,Gene Expression Regulation, Neoplastic ,Interferon-gamma ,Jurkat Cells ,HEK293 Cells ,A549 Cells ,Tumor Microenvironment ,Humans ,Indoleamine-Pyrrole 2,3,-Dioxygenase - Abstract
Programmed death ligand-1 (PD-L1) and indoleamine 2, 3-dioxygenase 1 (IDO1) are immune checkpoints induced by interferon-γ (IFN-γ) in the tumor microenvironment, leading to immune escape of tumors. Myricetin (MY) is a flavonoid distributed in many edible and medicinal plants. In this study, MY was identified to inhibit IFN-γ-induced PD-L1 expression in human lung cancer cells. It also reduced the expression of IDO1 and the production of kynurenine which is the product catalyzed by IDO1, while didn't show obvious effect on the expression of major histocompatibility complex-I (MHC-I), a crucial molecule for antigen presentation. In addition, the function of T cells was evaluated using a co-culture system consist of lung cancer cells and the Jurkat-PD-1 T cell line overexpressing PD-1. MY restored the survival, proliferation, CD69 expression and interleukin-2 (IL-2) secretion of Jurkat-PD-1 T cells suppressed by IFN-γ-treated lung cancer cells. Mechanistically, IFN-γ up-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis, which was targeted and inhibited by MY. Together, our research revealed a new mechanism of MY mediated anti-tumor activity and highlighted the potential implications of MY in tumor immunotherapy.
- Published
- 2022
3. Induction of an MLKL mediated non-canonical necroptosis through reactive oxygen species by tanshinol A in lung cancer cells
- Author
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Xiuping Chen, Ying Hou, Jin-Jian Lu, Bo Liu, Hongwei Gao, Yulin Feng, Qiongming Xu, Xin Liu, and Yiying Zhang
- Subjects
0301 basic medicine ,Programmed cell death ,Lung Neoplasms ,Necroptosis ,Apoptosis ,Biochemistry ,Cell membrane ,03 medical and health sciences ,0302 clinical medicine ,Caffeic Acids ,Cytosol ,Cell Line, Tumor ,medicine ,Humans ,Phosphorylation ,Pharmacology ,chemistry.chemical_classification ,Reactive oxygen species ,Cell Death ,Kinase ,Cell Membrane ,Pyroptosis ,Cell biology ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,A549 Cells ,030220 oncology & carcinogenesis ,Enzyme Induction ,Calcium ,Reactive Oxygen Species ,Protein Kinases ,Intracellular - Abstract
Recent discoveries revealed several types of programmed necrosis, such as necroptosis, ferroptosis, pyroptosis, etc. Necroptosis is mediated by signaling complexes with receptor-interacting protein kinases (RIPs) and mixed lineage kinase domain-like protein (MLKL). Here, we described an MLKL mediated non-canonical necroptosis through reactive oxygen species (ROS) in lung cancer cells triggered by a natural compound, tanshinol A (TSA). Morphologically, TSA-induced necrotic cell death is characterized by increased cell volume, transparent of cytoplasm, and rupture of the cell membrane. Biochemically, it induces intracellular ATP depletion and PI penetration. Molecularly, TSA-induced cell death is mediated by MLKL but independent of RIP1 and RIP3. Furthermore, TSA induces MLKL phosphorylation and membrane translocation, and cytosolic calcium accumulation. However, calcium shows no effect on TSA-induced cell death. Especially, TSA induces intracellular ROS generation, which was found to be the upstream of MLKL. Collectively, our data indicated that TSA triggers a novel type of programmed necrosis mediated by MLKL in lung cancer cells, which might have therapeutic potentials for lung cancer treatment.
- Published
- 2019
4. Activation of notch 3/c-MYC/CHOP axis regulates apoptosis and promotes sensitivity of lung cancer cells to mTOR inhibitor everolimus
- Author
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Hong Zhu, Zheng-Hai Tang, Xiao-Ming Jiang, Tao Yuan, Yu-Lian Xu, Ting Li, Xia Guo, Xiao-Huang Xu, Le-Le Zhang, Jia-Jie Shi, Xiuping Chen, and Jin-Jian Lu
- Subjects
0301 basic medicine ,Lung Neoplasms ,Antineoplastic Agents ,Apoptosis ,CHOP ,Biochemistry ,Stephania tetrandra ,03 medical and health sciences ,0302 clinical medicine ,Notch 3 ,Transcription (biology) ,Cell Line, Tumor ,medicine ,Humans ,Everolimus ,Lung cancer ,Receptor, Notch3 ,PI3K/AKT/mTOR pathway ,Pharmacology ,biology ,Chemistry ,TOR Serine-Threonine Kinases ,biology.organism_classification ,medicine.disease ,DNA-Binding Proteins ,HEK293 Cells ,030104 developmental biology ,A549 Cells ,Drug Resistance, Neoplasm ,030220 oncology & carcinogenesis ,Cancer research ,Transcription Factor CHOP ,Transcription Factors ,medicine.drug - Abstract
The mammalian target of rapamycin (mTOR) pathway converges diverse environmental cues to support the lung cancer growth and survival. However, the mTOR-targeted mono-therapy does not achieve expected therapeutic effect. Here, we revealed that fangchinoline (FCL), an active alkaloid that purified from the traditional Chinese medicine Stephania tetrandra S. Moore, enhanced the anti-lung cancer effect of mTOR inhibitor everolimus (EVE). The combination of EVE and FCL was effective to activate Notch 3, and subsequently evoked its downstream target c-MYC. The blockage of Notch 3 signal by the molecular inhibitor of γ-secretase or siRNA of Notch 3 reduced the c-MYC expression and attenuated the combinational efficacy of EVE and FCL on cell apoptosis and proliferation. Moreover, the c-MYC could bind to the C/EBP homologous protein (CHOP) promoter and facilitate CHOP transcription. The conditional genetic deletion of CHOP reduced the apoptosis on lung cancer cells to the same degree as blockage of Notch 3/c-MYC axis, providing further evidence for that the Notch 3/c-MYC axis regulates the transcription of CHOP and finally induces apoptosis upon co-treatment of FCL and EVE in lung cancer cells. Overall, our findings, to the best of our knowledge, firstly link CHOP to Notch 3/c-MYC axis-dependent apoptosis and provide the Notch 3/c-MYC/CHOP activation as a promising strategy for mTOR-targeted combination therapy in lung cancer treatment.
- Published
- 2020
5. O43 The effects and mechanisms of two main constituents from Glycyrrhiza uralensis Fisch-induced autophagy in non-small cell lung cancer
- Author
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Zheng-Hai Tang, Xiuping Chen, Jin-Jian Lu, Xin Chen, Yitao Wang, and Le-Le Zhang
- Subjects
Pharmacology ,Gene knockdown ,genetic structures ,biology ,Licochalcone A ,Glycyrrhiza uralensis ,Autophagy ,Cell ,Transfection ,CHOP ,biology.organism_classification ,Biochemistry ,eye diseases ,chemistry.chemical_compound ,medicine.anatomical_structure ,chemistry ,Apoptosis ,Cancer research ,medicine - Abstract
The Glycyrrhiza uralensis Fisch, one of the famous Chinese medicinal herbs, has been widely used in anti-cancer prescription. We found that glycerrhetinic acid (GA, triterpenoid) and licochalcone A (LCA, flavonoid), two primary constituents of Glycyrrhiza uralensis Fisch, induced cell proliferative inhibition, apoptosis, and autophagy in non-small cell lung cancer (NSCLC) A549 and NCI-H1299 cells. Combined treatment with chloroquine further enhanced GA- or LCA-induced expression of LC3-II and more red-fluorescent puncta than green ones were observed in GA- or LCA-treated cells with transfection of mRFP-EGFP-LC3, suggesting that GA and LCA induces autophagic flux in NSCLC cells. Inhibition of autophagy enhanced GA-induced cell proliferative inhibition and apoptosis in NSCLC cells. In contrast, LCA-induced cell proliferative inhibition and apoptosis were not significantly altered after autophagy inhibition in NSCLC cells. The JNK and IRE1 α were activated after incubation with GA. Pretreatment with the JNK inhibitor SP600125 or silencing of the JNK pathway by siRNA of JNK or c-jun decreased GA-induced autophagy. Moreover, the GA-induced JNK pathway activation and autophagy were decreased by IRE1α knockdown, suggesting that GA induces autophagy through activation of IRE1α-JNK/c-jun pathway. LCA increased the expression of CHOP, and knockdown of CHOP reversed LCA-induced autophagy, suggesting that LCA-induced autophagy is due to induction of CHOP expression. Collectively, both GA and LCA induced cell proliferative inhibition, apoptosis, and autophagy in NSCLC, and inhibition of autophagy might be an effective strategy to enhance the anti-NSCLC effects of Glycyrrhiza uralensis Fisch contained prescriptions.
- Published
- 2017
6. Dihydroartemisinin accelerates c-MYC oncoprotein degradation and induces apoptosis in c-MYC-overexpressing tumor cells
- Author
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Jian Ding, Linghua Meng, Uma Shankavaram, Li Ping Lin, Jin-Jian Lu, Guang Chen, John N. Weinstein, Cai Hua Zhu, and Lin Jiang Tong
- Subjects
Leupeptins ,medicine.medical_treatment ,Dihydroartemisinin ,Down-Regulation ,Apoptosis ,HL-60 Cells ,Biology ,Cysteine Proteinase Inhibitors ,Biochemistry ,Proto-Oncogene Proteins c-myc ,Antimalarials ,Glycogen Synthase Kinase 3 ,Mice ,GSK-3 ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Pharmacology ,Gene knockdown ,Glycogen Synthase Kinase 3 beta ,G1 Phase ,HCT116 Cells ,In vitro ,Artemisinins ,Cell culture ,Cancer cell ,Proteasome inhibitor ,Cancer research ,NIH 3T3 Cells ,Lithium Chloride ,medicine.drug - Abstract
Artemisinin and its derivatives (ARTs) are effective antimalarial drugs and also possess profound anticancer activity. However, the mechanism accounted for its distinctive activity in tumor cells remains unelucidated. We computed Pair wise Pearson correlation coefficients to identify genes that show significant correlation with ARTs activity in NCI-55 cell lines using data obtained from studies with HG-U133A Affymetrix chip. We found c-myc is one of the genes that showed the highest positive correlation coefficients among the probe sets analyzed (r=0.585, P
- Published
- 2009
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