Journal
CANCERS
Volume 12, Issue 3, Pages -Publisher
MDPI
DOI: 10.3390/cancers12030727
Keywords
natural bioactive compound; gallic acid; EGFR signaling; p53; PD-L1; immunotherapy
Categories
Funding
- National Research Foundation of Korea (NRF) - Korea government (MSIT) [2018R1C1B6006146]
- Basic Science Research Program through the National Research Foundation of Korea (NRF) - Ministry of Education [2019R1I1A1A01060399, 2019R1I1A1A01060537]
Ask authors/readers for more resources
Non-small-cell lung cancer (NSCLC) is the most common lung cancer subtype and accounts for more than 80% of all lung cancer cases. Epidermal growth factor receptor (EGFR) phosphorylation by binding growth factors such as EGF activates downstream prooncogenic signaling pathways including KRAS-ERK, JAK-STAT, and PI3K-AKT. These pathways promote the tumor progression of NSCLC by inducing uncontrolled cell cycle, proliferation, migration, and programmed death-ligand 1 (PD-L1) expression. New cytotoxic drugs have facilitated considerable progress in NSCLC treatment, but side effects are still a significant cause of mortality. Gallic acid (3,4,5-trihydroxybenzoic acid; GA) is a phenolic natural compound, isolated from plant derivatives, that has been reported to show anticancer effects. We demonstrated the tumor-suppressive effect of GA, which induced the decrease of PD-L1 expression through binding to EGFR in NSCLC. This binding inhibited the phosphorylation of EGFR, subsequently inducing the inhibition of PI3K and AKT phosphorylation, which triggered the activation of p53. The p53-dependent upregulation of miR-34a induced PD-L1 downregulation. Further, we revealed the combination effect of GA and anti-PD-1 monoclonal antibody in an NSCLC-cell and peripheral blood mononuclear-cell coculture system. We propose a novel therapeutic application of GA for immunotherapy and chemotherapy in NSCLC.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available