Unknown

Dataset Information

0

The histone deacetylase inhibitor cambinol prevents acidic pHe-induced anterograde lysosome trafficking independently of sirtuin activity.


ABSTRACT: Common features of the solid tumor microenvironment, such as acidic extracellular pH and growth factors, are known to induce the redistribution of lysosomes from a perinuclear region to a position near the plasma membrane. Lysosome/plasma membrane juxtaposition facilitates invasion by allowing for the release of lysosomal proteases, including cathepsin B, which contribute to matrix degradation. In this study we identified the sirtuin 1/sirtuin 2 (SIRT1/2) inhibitor cambinol acts as a drug that inhibits lysosome redistribution and tumor invasion. Treatment of cells with cambinol resulted in a juxtanuclear lysosome aggregation (JLA) similar to that seen upon treatment with the PPAR? agonist, troglitazone (Tro). Like Tro, cambinol required the activity of ERK1/2 in order to induce this lysosome clustering phenotype. However, cambinol did not require the activity of Rab7, suggesting that this drug causes JLA by a mechanism different from what is known for Tro. Additionally, cambinol-induced JLA was not a result of autophagy induction. Further investigation revealed that cambinol triggered JLA independently of its activity as a SIRT1/2 inhibitor, suggesting that this drug could have effects in addition to SIRT1/2 inhibition that could be developed into a novel anti-cancer therapy.

SUBMITTER: Dykes SS 

PROVIDER: S-EPMC5668693 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

altmetric image

Publications

The histone deacetylase inhibitor cambinol prevents acidic pH<sub>e</sub>-induced anterograde lysosome trafficking independently of sirtuin activity.

Dykes Samantha S SS   Friday Ellen E   Pruitt Kevin K   Cardelli James A JA  

Biochemistry and biophysics reports 20150726


Common features of the solid tumor microenvironment, such as acidic extracellular pH and growth factors, are known to induce the redistribution of lysosomes from a perinuclear region to a position near the plasma membrane. Lysosome/plasma membrane juxtaposition facilitates invasion by allowing for the release of lysosomal proteases, including cathepsin B, which contribute to matrix degradation. In this study we identified the sirtuin 1/sirtuin 2 (SIRT1/2) inhibitor cambinol acts as a drug that i  ...[more]

Similar Datasets

| S-EPMC4728416 | biostudies-literature
| S-EPMC1525231 | biostudies-literature
| S-EPMC2844323 | biostudies-literature
| S-EPMC2168398 | biostudies-literature
| S-EPMC7787271 | biostudies-literature
| S-EPMC1800606 | biostudies-literature
| S-EPMC8572779 | biostudies-literature
| S-EPMC9238633 | biostudies-literature
| S-EPMC3967972 | biostudies-literature
| S-EPMC5036044 | biostudies-literature