Home Blog of Signal Transduction Metabolism Peroxidases Acid-Responsive Micelles Releasing Cinnamaldehyde Enhance RSL3-Induced Ferroptosis in Tumor Cells

Category

Archives

Popular Post

ESKM, a novel therapeutic agent for sensitive and resistant PH+ leukemias

The mechanism of resistance to JAK2 inhibitor in myeloproliferative neoplasms patients

Effects of PARP inhibitors in BRCA gene-mutated ovarian cancer

DASATINIB; An inhibitor of Receptor Tyrosine Kinase

GP130/JAK/STAT3 signaling pathway induces multiple myeloma

Acid-Responsive Micelles Releasing Cinnamaldehyde Enhance RSL3-Induced Ferroptosis in Tumor Cells

Ferroptosis is a novel type of regulated cell death characterized by the accumulation of lipid peroxides to lethal levels. Most tumor cells are extremely vulnerable to ferroptosis due to the high levels of reactive oxygen species (ROS) produced by their active metabolism. Therefore, tumor cells rely on glutathione (GSH) to reduce lipid peroxides catalyzed by glutathione peroxidase 4 (GPX4), and this pathway is also an important target for a variety of drugs that promote tumor cell ferroptosis. Herein, RSL3@PCA was designed to simultaneously deplete intracellular GSH and inhibit the activity of GPX4, thereby significantly promoting tumor cell ferroptosis. RSL3@PCA was successfully prepared by encapsulating a selective inhibitor of GPX4 into acid-responsive nanoparticle PCA. After being taken up by tumor cells, the acid-responsive nanoparticle gradually degraded to release cinnamaldehyde (CA) and the encapsulated RSL3. CA and RSL3 block the reduction of lipid peroxides in cells, thereby inducing ferroptosis. By a cytotoxicity assay and 4T1 cell xenotransplantation model, we confirmed that RSL3@PCA has excellent inhibition of tumor growth without significant toxicity to normal cells and tissues and still has a good therapeutic effect on tumor cells that are resistant to conventional chemotherapy drugs. This work provides new drug combinations for promoting ferroptosis in tumor cells without severe side effects in normal organs.

Related Products

Cat.No. Product Name Information
S8155 RSL3 RSL3 ((1S,3R)-RSL3) is a ferroptosis activator in a VDAC-independent manner,exhibiting selectivity for tumor cells bearing oncogenic RAS. RSL3 binds, inactivates GPX4 and thus mediates GPX4-regulated ferroptosis.

Related Targets

Peroxidases Ferroptosis