Rutecarpine Suppresses Non‐Small Cell Lung Cancer Progression Through Activating the STING Pathway and Elevating CD8+ T Cells

Chemical Biology & Drug Design, Journal Year: 2025, Volume and Issue: 105(2)

Published: Feb. 1, 2025

ABSTRACT Globally, non‐small cell lung cancer (NSCLC) is the primary cause of cancer‐related deaths. Rutecarpine (RUT), a quinazolinocarboline alkaloid that naturally occurring and present in Chinese medicinal herbs, has been shown to have anticancer properties several lines. However, specific antitumor mechanisms RUT NSCLC remain unclear. This study demonstrates induces apoptosis significantly reduces viability effect achieved by stimulating intracellular ROS production, leading mitochondrial dysfunction. The decreased observed with treatment attributed elimination through suppression N‐acetylcysteine (NAC). Furthermore, therapy elevated production CXCL10 CCL5 lines markedly activated STING pathway cells. Mechanistically, substantially levels PD‐L1 protein Notably, vivo experiments demonstrated inhibits mouse tumor growth mice, exhibiting anti‐tumor activity elevating CD8 + T These findings strongly support as promising anti‐cancer drug for NSCLC.

Language: Английский

Embryonic lethal abnormal vision like 1-stabilized histone deacetylase 6 promotes hepatic stellate cell activation to accelerate liver fibrosis progression through ribosomal protein S5 downregulation

CytoJournal, Journal Year: 2025, Volume and Issue: 22, P. 30 - 30

Published: March 6, 2025

Histone deacetylase 6 (HDAC6) has been confirmed to participate in the regulation of liver fibrosis (LF) progression. This study aims explore role and mechanism HDAC6 LF process. Serum samples were collected from cirrhosis (LC) patients normal healthy individuals. Human hepatic stellate cells (HSC; LX-2) stimulated with transforming growth factor β1 (TGF-β1) mimic cell models. The levels HDAC6, ribosomal protein S5 (RPS5), embryonic lethal abnormal vision like 1 (ELAVL1), fibrosis-related markers determined by quantitative real-time polymerase chain reaction or western blot. Cell proliferation invasion detected using counting kit 8 assay, 5-ethynyl-2'-deoxyuridine Transwell assay. contents inflammatory factors examined enzyme-linked immunosorbent Furthermore, co-immunoprecipitation RNA immunoprecipitation assays performed assess interaction between RPS5 ELAVL1. effect ELAVL1 knockdown on mRNA stability was evaluated Actinomycin D treatment showed increased expression LC patients. reduced TGF-β1-induced LX-2 proliferation, invasion, fibrosis, inflammation. Moreover, acetylation RPS5, reversed inhibition si-HDAC6 Meanwhile, interacted stabilize its mRNA, thus inhibiting expression. Our data revealed that ELAVL1-stabilized promoted HSC activation repressing acetylation, providing a novel target for alleviating

Language: Английский