EMAIL THIS PAGE TO A FRIEND

Autophagy

Elaiophylin, a novel autophagy inhibitor, exerts antitumor activity as a single agent in ovarian cancer cells.


PMID 25893854

Abstract

Currently, targeting the autophagic pathway is regarded as a promising new strategy for cancer drug discovery. Here, we screened the North China Pharmaceutical Group Corporation's pure compound library of microbial origin using GFP-LC3B-SKOV3 cells and identified elaiophylin as a novel autophagy inhibitor. Elaiophylin promotes autophagosome accumulation but blocks autophagic flux by attenuating lysosomal cathepsin activity, resulting in the accumulation of SQSTM1/p62 in various cell lines. Moreover, elaiophylin destabilizes lysosomes as indicated by LysoTracker Red staining and CTSB/cathepsin B and CTSD/ cathepsin D release from lysosomes into the cytoplasm. Elaiophylin eventually decreases cell viability, especially in combination with cisplatin or under hypoxic conditions. Furthermore, administration of a lower dose (2xa0mg/kg) of elaiophylin as a single agent achieves a significant antitumor effect without toxicity in an orthotopic ovarian cancer model with metastasis; however, high doses (8xa0mg/kg) of elaiophylin lead to dysfunction of Paneth cells, which resembles the intestinal phenotype of ATG16L1-deficient mice. Together, these results provide a safe therapeutic window for potential clinical applications of this compound. Our results demonstrate, for the first time, that elaiophylin is a novel autophagy inhibitor, with significant antitumor efficacy as a single agent or in combination in human ovarian cancer cells, establishing the potential treatment of ovarian cancer by this compound.

Related Materials

Product #

Image

Description

Molecular Formula

Add to Cart

SAB1405470
Anti-BIRC5 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
HPA002830
Anti-BIRC5 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB3500285
Anti-LAMP-1 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
L1418
Anti-LAMP1 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
HPA014750
Anti-LAMP1 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
SAB4200361
Anti-LC3B antibody, Mouse monoclonal, clone LC3B-6, purified from hybridoma cell culture
SAB2700738
Anti-Map1lc3b antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB3501065
Anti-MAP1LC3B antibody produced in rabbit, affinity isolated antibody
SAB1406748
Anti-SQSTM1 antibody produced in mouse, purified immunoglobulin, buffered aqueous solution
SAB3500430
Anti-SQSTM1 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB2104334
Anti-SQSTM1 antibody produced in rabbit, affinity isolated antibody
S8191
Anti-Survivin antibody produced in rabbit, IgG fraction of antiserum, buffered aqueous solution
SAB3500269
Anti-Survivin antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
SAB4501460
Anti-Survivin antibody produced in rabbit, affinity isolated antibody
SAB1401521
Anti-TUBA1B antibody produced in rabbit, purified immunoglobulin, buffered aqueous solution
SAB3500594
Anti-ZIP3 antibody produced in rabbit, affinity isolated antibody, buffered aqueous solution
LYSISO1 Lysosome Isolation Kit, sufficient for 25 g (tissue), sufficient for 20 mL (packed cells), enrichment of lysosomes from tissues and packed cells
WH0000332M1
Monoclonal Anti-BIRC5 antibody produced in mouse, clone 5B10, purified immunoglobulin, buffered aqueous solution
SAB4100131
Monoclonal Anti-BIRC5 antibody produced in mouse, clone BIRC5-A113, culture supernatant
SAB5300510 Monoclonal Anti-BIRC5 antibody produced in mouse, clone 2H5H2, ascites fluid
SAB5300511
Monoclonal Anti-BIRC5 antibody produced in mouse, clone 1H5, purified immunoglobulin, buffered aqueous solution
WH0010376M1
Monoclonal Anti-K-ALPHA-1 antibody produced in mouse, clone 4D1, purified immunoglobulin, buffered aqueous solution
WH0081631M1
Monoclonal Anti-MAP1LC3B antibody produced in mouse, clone 4E11, purified immunoglobulin, buffered aqueous solution
SAB1405293
Monoclonal Anti-MAP1LC3B antibody produced in mouse, clone 4G7, purified immunoglobulin, buffered aqueous solution
WH0008878M1
Monoclonal Anti-SQSTM1 antibody produced in mouse, clone 2C11, purified immunoglobulin, buffered aqueous solution
SAB1404647
Monoclonal Anti-SQSTM1 antibody produced in mouse, clone 1C9, purified immunoglobulin, buffered aqueous solution
SAB1404816
Monoclonal Anti-TUBA1B antibody produced in mouse, clone 2E8, purified immunoglobulin, buffered aqueous solution
P0044 Phosphatase Inhibitor Cocktail 3, DMSO solution