Single amino acid arginine deprivation triggers prosurvival autophagic response in ovarian carcinoma SKOV3.

Abstract

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.

• Authors: Galyna Shuvayeva, Yaroslav Bobak, Natalia Igumentseva, Rossella Titone, Federica Morani, Oleh Stasyk, Ciro Isidoro
• Journal: BioMed research international (Biomed Res Int) Vol. 2014 Pg. 505041 ( 2014) ISSN: 2314-6141 [Electronic] United States
• PMID: 24987688 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Apoptosis Regulatory Proteins
• BECN1 protein, human
• Beclin-1
• Membrane Proteins
• Neoplasm Proteins
• Arginine

Topics

• Apoptosis Regulatory Proteins (metabolism)
• Arginine
• Autophagy
• Beclin-1
• Cell Line, Tumor
• Cell Survival
• Female
• Humans
• Membrane Proteins (metabolism)
• Neoplasm Proteins (metabolism)
• Ovarian Neoplasms (metabolism, pathology, therapy)