Immune Checkpoint PD-1/PD-L1 CTLA-4/CD80 are Blocked by Rhus verniciflua Stokes and its Active Compounds

Li, Wei; Kim, Tae-In; Kim, Ji Hye; Chung, Hwan‐Suck

doi:10.3390/molecules24224062

Cited by 42 publications

(34 citation statements)

References 37 publications

(38 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When programmed death-ligand 1 (PD-L1)-a protein present on the surface of tumor cells-binds the PD-1, the signal is sent to suppress the immune system response; therefore, the inhibitors of PD-L1/PD-1 signaling pathway could be promising agents in cancer immunotherapy [141]. The studies on flavonoids as possible suppressors of PD-L1/PD-1 immune checkpoint have not been very intense yet, nevertheless the first encouraging results were obtained demonstrating the inhibition of PD-L1 expression by flavone apigenin in A375 melanoma cells [142] and PD-1/PD-L1 inhibition in vitro by flavonols quercetin [143] and fisetin [143] as well as isoflavonoid glyasperin C [144].…”

Section: Immunomodulatory and Anti-inflammatory Effects Of Flavonoidsmentioning

confidence: 99%

Flavonoids as Anticancer Agents

et al. 2020

View full text Add to dashboard Cite

Flavonoids are polyphenolic compounds subdivided into 6 groups: isoflavonoids, flavanones, flavanols, flavonols, flavones and anthocyanidins found in a variety of plants. Fruits, vegetables, plant-derived beverages such as green tea, wine and cocoa-based products are the main dietary sources of flavonoids. Flavonoids have been shown to possess a wide variety of anticancer effects: they modulate reactive oxygen species (ROS)-scavenging enzyme activities, participate in arresting the cell cycle, induce apoptosis, autophagy, and suppress cancer cell proliferation and invasiveness. Flavonoids have dual action regarding ROS homeostasis—they act as antioxidants under normal conditions and are potent pro-oxidants in cancer cells triggering the apoptotic pathways and downregulating pro-inflammatory signaling pathways. This article reviews the biochemical properties and bioavailability of flavonoids, their anticancer activity and its mechanisms of action.

show abstract

Section: Immunomodulatory and Anti-inflammatory Effects Of Flavonoidsmentioning

confidence: 99%

Flavonoids as Anticancer Agents

et al. 2020

View full text Add to dashboard Cite

show abstract

“…To examine the effect of test samples on PD-1/PD-L1 interaction, PD-1/PD-L1 Competitive ELISA kits were performed by the distributor's manuals [13]. In a brief, recombinant hPD-L1 protein was diluted at 1 µg/mL in phosphate-buffered saline (PBS, pH 7.4) and then was coated in 96-well white plates at 4 • C overnight.…”

Section: Pd-1/pd-l1 Competitive Elisamentioning

confidence: 99%

Unripe Black Raspberry (Rubus coreanus Miquel) Extract and Its Constitute, Ellagic Acid Induces T Cell Activation and Antitumor Immunity by Blocking PD-1/PD-L1 Interaction

Kim

et al. 2020

Foods

Self Cite

View full text Add to dashboard Cite

Rubus coreanus Miquel (R. coreanus) is a unripen fruit of black raspberry native to eastern Asia. It is used as traditional oriental medicine and supplementary foods for centuries. Previous studies have shown that the R. coreanus extract (RCE) and its main constitute ellagic acid possess diverse biological activities. However, the effects of RCE on antitumor immunity and T cell function were not fully understood. The present study describes the anti-tumor effect of RCE in humanized PD-1 mice by blocking PD-1/PD-L1 interaction. Competitive enzyme-linked immunosorbent assay (ELISA) and pull down assay were performed to elucidate the binding properties of RCE in vitro. Cellular PD-1/PD-L1 blockade activities were measured by T cell receptor (TCR)-induced nuclear factor of activated T cells-luciferase activity in co-cultured cell models with PD-1/NFAT Jurkat and PD-L1/aAPC CHO-K1 cells. The in vivo efficacy of RCE was confirmed in humanized PD-1 mice bearing MC38 colorectal tumor. RCE and ellagic acid dose-dependently block the binding of PD-1 to PD-L1. Moreover, oral administration of RCE showed the potent anti-tumor activity similar to anti-PD-1 antibody. The present study suggests that RCE possesses potent anti-tumor effect via PD-1/PD-L1 blockade, and ellagic acid is the main compound in RCE. Thus, we provide new aspects of RCE as an immunotherapeutic agent.

show abstract

“…In a high-fat diet-induced obesity mouse model, resveratrol significantly reduced CTLA-4 expression in regulatory T cells [ 161 ], demonstrating results similar to those reported elsewhere in an inflammatory bowel disease model [ 162 , 163 ]. Furthermore, studies show that active compounds in Rhus verniciflua Stokes extract, used in Korean herbal medicine, successfully blocked the expression of both PD-1/PDL-1 and CTLA-4 [ 164 , 165 , 166 ].…”

Section: Phytochemicalsmentioning

confidence: 99%

Phytochemical Targeting of STAT3 Orchestrated Lipid Metabolism in Therapy-Resistant Cancers

et al. 2020

View full text Add to dashboard Cite

Lipids are critical for maintaining homeostasis and cellular metabolism. However, the dysregulation of lipid metabolism contributes to the pathogenesis of chronic inflammatory diseases and is a hallmark of several cancer types. Tumours exist in a microenvironment of poor vascularization-depleted oxygen and restricted nutrients. Under these conditions, tumours have been shown to increasingly depend on the metabolism of fatty acids for sustained proliferation and survival. Signal transducer and activator of transcription 3 (STAT3) plays a key role in cellular processes such as cell growth, apoptosis and lipid metabolism. Aberrant STAT3 activity, as seen in several cancer types, is associated with tumour progression and malignancy, in addition to propagating crosstalk between tumour cells and the microenvironment. Furthermore, STAT3-regulated lipid metabolism is critical for cancer stem cell self-renewal and therapy resistance. Plant-derived compounds known as phytochemicals are a potential source for novel cancer therapeutic drugs. Dietary phytochemicals are known to modulate key cellular signalling pathways involved in lipid homeostasis and metabolism, including the STAT3 signalling pathways. Targeting STAT3 orchestrated lipid metabolism has shown therapeutic promise in human cancer models. In this review, we summarize the antitumour activity of phytochemicals with an emphasis placed on their effect on STAT3-regulated lipid metabolism and their role in abrogating therapy resistance.

show abstract

Immune Checkpoint PD-1/PD-L1 CTLA-4/CD80 are Blocked by Rhus verniciflua Stokes and its Active Compounds

Cited by 42 publications

References 37 publications

Flavonoids as Anticancer Agents

Flavonoids as Anticancer Agents

Unripe Black Raspberry (Rubus coreanus Miquel) Extract and Its Constitute, Ellagic Acid Induces T Cell Activation and Antitumor Immunity by Blocking PD-1/PD-L1 Interaction

Phytochemical Targeting of STAT3 Orchestrated Lipid Metabolism in Therapy-Resistant Cancers

Contact Info

Product

Resources

About