The Poly (ADP-Ribose) Polymerase Inhibitor Veliparib and Radiation Cause Significant Cell Line Dependent Metabolic Changes in Breast Cancer Cells.
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.
Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.
Vijesh J
VJ
Bhute
Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.
Yan
Y
Ma
Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.
Xiaoping
X
Bao
Department of Chemical and Biological Engineering, University of Wisconsin-Madison, Madison, WI 53706, USA.
Sean P
SP
Palecek
D000596:Amino Acids / Q000378:metabolism; D001562:Benzimidazoles / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000532:radiotherapy*; D045744:Cell Line, Tumor; D003401:Creatine / Q000378:metabolism; D004249:DNA Damage; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D009682:Magnetic Resonance Spectroscopy; D053858:Metabolic Networks and Pathways / Q000187:drug effects / Q000528:radiation effects; D008928:Mitochondria / Q000187:drug effects; D009243:NAD / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000627:therapeutic use*
D000596:Amino Acids; D001562:Benzimidazoles; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; C521013:veliparib; D009243:NAD; D005978:Glutathione; D003401:Creatine