Honokiol Enhances TRAIL-Mediated Apoptosis through STAMBPL1-Induced Survivin and c-FLIP Degradation.
Honokiol is a natural biphenolic compound extracted from traditional Chinese medicine Magnolia species, which have been known to display various biological effects including anti-cancer, anti-proliferative, anti-angiogenic, and anti-metastatic activities in cancer cells. Here, we found that honokiol sensitizes cancer cells to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through downregulation ... of anti-apoptotic proteins survivin and c-FLIP. Ectopic expression of survivin and c-FLIP markedly abolished honokiol and TRAIL-induced apoptosis. Mechanistically, honokiol induced protein degradation of c-FLIP and survivin through STAMBPL1, a deubiquitinase. STAMBPL1 interacted with survivin and c-FLIP, resulted in reduction of ubiquitination. Knockdown of STAMBPL1 reduced survivin and c-FLIP protein levels, while overexpression of STAMBPL1 inhibited honokinol-induced survivin and c-FLIP degradation. Our findings provided that honokiol could overcome TRAIL resistance through survivin and c-FLIP degradation induced by inhibition of STAMBPL1 expression.
Mesh Terms:
Antineoplastic Agents, Phytogenic, Apoptosis, Apoptosis Regulatory Proteins, Biphenyl Compounds, CASP8 and FADD-Like Apoptosis Regulating Protein, Cell Line, Tumor, Gene Knockdown Techniques, Humans, Lignans, Peptide Hydrolases, Plant Extracts, Survivin, TNF-Related Apoptosis-Inducing Ligand, Ubiquitination
Antineoplastic Agents, Phytogenic, Apoptosis, Apoptosis Regulatory Proteins, Biphenyl Compounds, CASP8 and FADD-Like Apoptosis Regulating Protein, Cell Line, Tumor, Gene Knockdown Techniques, Humans, Lignans, Peptide Hydrolases, Plant Extracts, Survivin, TNF-Related Apoptosis-Inducing Ligand, Ubiquitination
Biomolecules
Date: Dec. 06, 2018
PubMed ID: 31817770
View in: Pubmed Google Scholar
Download Curated Data For This Publication
224927
Switch View:
- Interactions 2