Work

The Poly (ADP-Ribose) Polymerase Inhibitor Veliparib and Radiation Cause Significant Cell Line Dependent Metabolic Changes in Breast Cancer Cells

Year: 2016

Type: article

Abstract: Breast tumors are characterized into subtypes based on their surface marker expression, which affects their prognosis and treatment. Poly (ADP-ribose) polymerase (PARP) inhibitors have shown promising results in clinical trials, both as single agents and in combination with other chemotherapeutics, in several subtypes of breast cancer patients. Here, we used NMR-based metabolomics to probe cell line-specific effects of the PARP inhibitor Veliparib and radiation on metabolism in three breast cancer cell lines. Our data reveal several cell line-independent metabolic changes upon PARP inhibition. Pathway enrichment and topology analysis identified that nitrogen metabolism, glycine, serine and threonine metabolism, aminoacyl-tRNA biosynthesis and taurine and hypotaurine metabolism were enriched after PARP inhibition in all three breast cancer cell lines. Many metabolic changes due to radiation and PARP inhibition were cell line-dependent, highlighting the need to understand how these treatments affect cancer cell response via changes in metabolism. Finally, both PARP inhibition and radiation induced a similar metabolic responses in BRCA-mutant HCC1937 cells, but not in MCF7 and MDAMB231 cells, suggesting that radiation and PARP inhibition share similar interactions with metabolic pathways in BRCA mutant cells. Our study emphasizes the importance of differences in metabolic responses to cancer treatments in different subtypes of cancers.

Source: Scientific Reports

DOI: 10.1038/srep36061

Authors: Vijesh J. Bhute, Yan Ma, Xiaoping Bao, Sean P. Palecek

Institution: University of Wisconsin–Madison

Language: English

Topic: PARP inhibition in cancer therapy

Subfield: Oncology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,690