Saikosaponin A Mediates the Anti-Acute Myeloid Leukemia Effect via the P-JNK Signaling Pathway Induced by Endoplasmic Reticulum Stress

Drug Design Development and Therapy, Год журнала: 2025, Номер Volume 19, С. 1983 - 2001

Опубликована: Март 1, 2025

This study aims to investigate the antitumor effects of saikosaponin A (SSA) on acute myeloid leukemia (AML) and elucidate its underlying mechanisms, particularly focusing endoplasmic reticulum stress (ERS)-mediated MAPK-p-JNK signaling pathway. The inhibitory SSA proliferation AML cell lines K562 HL60 were evaluated using CCK8 EdU assays. Apoptotic induced by analyzed via flow cytometry. RNA sequencing was performed identify differentially expressed genes enriched pathways. Western blot analysis utilized confirm involvement ERS activation Further validation potential mechanism SSA-induced apoptosis conducted SP600125 4PBA. in vivo anti-AML efficacy assessed a xenograft model. exhibited significant HL60, with IC50 values at 12, 24, 48 hours demonstrating time- dose-dependency (19.84 μM, 17.86 15.38 μM for K562; 22.73 17.02 15.25 respectively). demonstrated that induces cells through mitochondrial apoptotic Transcriptomic profiling analyses confirmed activates ERS-mediated p-JNK pathway induce AML, process can be reversed addition 4PBA or SP600125. Furthermore, significantly reduced tumor volume weight NOD-SCID mouse model without causing notable toxicity liver, kidneys, lungs, heart, while also activating pathways vivo. pathway, exhibiting both vitro vivo, accompanied favorable safety profile.

Язык: Английский

Synthesis of a Capsule for the Targeted Delivery of Active Compounds Based on Metal-Organic Frameworks with a Modified Surface

Nanobiotechnology Reports, Год журнала: 2024, Номер 19(S1), С. S128 - S137

Опубликована: Дек. 1, 2024

Язык: Английский