Single amino acid arginine deprivation triggers prosurvival autophagic response in ovarian carcinoma SKOV3.
Galyna ShuvayevaYaroslav BobakNatalia IgumentsevaRossella TitoneFederica MoraniOleh StasykCiro IsidoroPublished in: BioMed research international (2014)
Autophagy is a process of cytosol-to-lysosome vesicle trafficking of cellular constituents for degradation and recycling of their building blocks. Autophagy becomes very important for cell viability under different stress conditions, in particular under amino acid limitation. In this report we demonstrate that single amino acid arginine deprivation triggers profound prosurvival autophagic response in cultured human ovarian cancer SKOV3 cells. In fact, a significant drop in viability of arginine-starved SKOV3 cells was observed when autophagy was inhibited by either coadministration of chloroquine or transcriptional silencing of the essential autophagy protein BECLIN 1. Enzymatic arginine deprivation is a novel anticancer therapy undergoing clinical trials. This therapy is considered nontoxic and selective, as it allows controlling the growth of malignant tumours deficient in arginine biosynthesis. We propose that arginine deprivation-based combinational treatments that include autophagy inhibitors (e.g., chloroquine) may produce a stronger anticancer effect as a second line therapy for a subset of chemoresistant ovarian cancers.
Keyphrases
- amino acid
- cell death
- cell cycle arrest
- endoplasmic reticulum stress
- induced apoptosis
- nitric oxide
- signaling pathway
- oxidative stress
- endothelial cells
- clinical trial
- randomized controlled trial
- autism spectrum disorder
- transcription factor
- single molecule
- fluorescent probe
- mesenchymal stem cells
- open label
- heat shock
- cell wall
- phase ii