OBJECTIVE Programmed death ligand-1(PD-L1)and indoleamine 2,3-dioxygenase 1(IDO1)are immune checkpoints which can be induced by interferon-γ(IFN-γ)in the tumor microenvironment,leading to immune escape of tumors.Myr...OBJECTIVE Programmed death ligand-1(PD-L1)and indoleamine 2,3-dioxygenase 1(IDO1)are immune checkpoints which can be 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.The aim of this study is to clarify the effect and the mechanism of MY on inhibiting IFN-γ-induced PD-L1 and IDO1 in lung cancer cells.METHODS Expressions of PD-L1 and major histocompatibility complex-I(MHC-I)were evaluated by flow cytometry and Western blotting,and the expression of IDO1 was measured by Western blotting.qRT-PCR was used to detect their mRNA levels.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 that overexpressing PD-1.Molecular docking analysis,Western blotting and immunofluorescence were used for mechanism study.RESULTS MY potently inhibited IFN-γ-induced PD-L1 and IDO1 expression in human lung cancer cells,while didn't show obvious effect on the expression of MHC-I.In addition,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 in the co-culture system.Mechanistically,IFN-γup-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis,which was targeted and inhibited by MY.CONCLUSION Our research revealed a new insight into the anti-tumor effects of MY which inhibited IFN-γ-induced PD-L1 and IDO1 expression,supporting the potential of MY in anti-tumor immunotherapy.展开更多
The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research.Frankincense,a widely recognized natural antitumor medicine,has undergone a systematic review en...The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research.Frankincense,a widely recognized natural antitumor medicine,has undergone a systematic review encompassing its species,chemical constituents,and diverse pharmacological activities and mechanisms.The different species of frankincense include Boswellia serrata,Somali frankincense,Boswellia frereana,and Boswellia arabica.Various frankincense extracts and compounds exhibit antitumor,anti-inflammatory,and hepatoprotective properties and antioxidation,memory enhancement,and immunological regulation capabilities.They also have comprehensive effects on regulating flora.Frankincense and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against tumors.This review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents,thus laying the foundations for developing effective tumor-combating targets.展开更多
基金Science and Technology Development Fund,Macao SAR(0129/2019/A3176/2017/A3)and University of Macao(MYRG2018-00165-ICMS)。
文摘OBJECTIVE Programmed death ligand-1(PD-L1)and indoleamine 2,3-dioxygenase 1(IDO1)are immune checkpoints which can be 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.The aim of this study is to clarify the effect and the mechanism of MY on inhibiting IFN-γ-induced PD-L1 and IDO1 in lung cancer cells.METHODS Expressions of PD-L1 and major histocompatibility complex-I(MHC-I)were evaluated by flow cytometry and Western blotting,and the expression of IDO1 was measured by Western blotting.qRT-PCR was used to detect their mRNA levels.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 that overexpressing PD-1.Molecular docking analysis,Western blotting and immunofluorescence were used for mechanism study.RESULTS MY potently inhibited IFN-γ-induced PD-L1 and IDO1 expression in human lung cancer cells,while didn't show obvious effect on the expression of MHC-I.In addition,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 in the co-culture system.Mechanistically,IFN-γup-regulated PD-L1 and IDO1 at the transcriptional level through the JAK-STAT-IRF1 axis,which was targeted and inhibited by MY.CONCLUSION Our research revealed a new insight into the anti-tumor effects of MY which inhibited IFN-γ-induced PD-L1 and IDO1 expression,supporting the potential of MY in anti-tumor immunotherapy.
基金Supported by the Youth Project of National Natural Science Foundation of China(No.82104861)National Natural Science Foundation of China(Nos.U20A20408 and 82074450)+1 种基金Natural Science Foundation of Hunan Province of China(Nos.2021JJ40408,2021JJ40420)Hunan Provincial Department of Education General Project(No.20C1407)。
文摘The discovery of novel antitumor agents derived from natural plants is a principal objective of anticancer drug research.Frankincense,a widely recognized natural antitumor medicine,has undergone a systematic review encompassing its species,chemical constituents,and diverse pharmacological activities and mechanisms.The different species of frankincense include Boswellia serrata,Somali frankincense,Boswellia frereana,and Boswellia arabica.Various frankincense extracts and compounds exhibit antitumor,anti-inflammatory,and hepatoprotective properties and antioxidation,memory enhancement,and immunological regulation capabilities.They also have comprehensive effects on regulating flora.Frankincense and its principal chemical constituents have demonstrated promising chemoprophylactic and therapeutic abilities against tumors.This review provides a systematic summary of the mechanism of action underlying the antitumor effects of frankincense and its major constituents,thus laying the foundations for developing effective tumor-combating targets.
