BCL-XL Protects ASS1-Deficient Cancers from Arginine Starvation-Induced Apoptosis.

ABSTRACT:

Purpose

Argininosuccinate synthetase 1 (ASS1) silencing in carcinomas and sarcomas leads to a dependence on extracellular arginine for survival. Arginine deprivation therapies, such as PEGylated arginine deiminase (ADI-PEG20), have shown limited effectiveness, which may be due to underlying mechanisms that inhibit apoptosis.

Experimental design

The effects of ADI-PEG20 on cell-cycle regulation, apoptosis, and BCL-XL-mediated survival pathways in ASS1-deficient cancer cells were determined. The mechanism of cell death protection was determined by assessing caspase and PARP cleavage, CDK2 activity, MCL1 expression, and the interactions among BCL-XL, BAX, and BAK. In vitro synergy was determined, and in vivo efficacy was modeled.

Results

Treatment with ADI-PEG20 led to r

SUBMITTER: Panda PK 

PROVIDER: S-EPMC11964295 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature