Thus our lipid metabolism derivatives are candidate biomarkers of the inflammation status. Lipid metabolism alterations that we observe at high dose CUR may be linked to NF-kB pathway. NF-kB is a transcription factor that regulates the transcription of many genes for immune response, cell adhesion, differentiation, proliferation, angiogenesis, and antiapoptosis. NF-kB activation is involved in multiple human pathologies including inflammatory diseases, immune deficiencies, diabetes, and atherosclerosis as well as oncogenesis. CUR has been reported to inhibit NF-kB, thus suppressing various cell survival and proliferative genes, resulting in anti-inflammatory effects. Therefore, at high dose, observed changes in tFA, PUF, GPC and GPE may indicate NFkB inhibition. Overall, metabolomics draws attention on the fact that associating CUR at in vivo-achievable dose to DTX may induce undesirable INCB18424 responses in breast cancer cells including proinflammatory and anti-oxidant effects. Therefore the combination needs further evaluation in terms of benefit-toxicity ratio because, although it may alleviate chemotherapy-related toxicity in normal cells, it may reduce chemotherapy efficacy in tumor cells. Some metabolites or metabolite subsets were found to behave biphasically, even hormetically, with dose or duration of association with DTX. Hormetic effects have been reported for cell proliferation with CUR dose. Also, hormetic effects have been described in response to CUR for metabolites or enzyme activities including GLO1, thioredoxin reductase and others. In addition, the disparity of GSH level and GST activity encountered at a single dose of CUR in various cell types may be explained by hormetic behavior. Molecular GW786034 pathways involved in hormetic response to stressing agents in tumor cells include p53-dependent apoptotic pathways, sphingomyelin metabolism pathway, Nrf2 transcription factor pathway, and others. In cotreatments of CUR with low dose DTX, metabolomics revealed a hormetic component with duration of exposure to CUR, the F2 axis of PCA, which was explained by accumulation of glucose metabolization products and diminished lipid content. These alterations at 24 h cotreatment, reverted from 48 h to 96 h, thus following a hormetic behavior. CUR was reported to activate the AMPK pathway The involvement of AMPK signaling could account for simultaneous increase in glycolysis and decreased fatty acid biosynthesis, or increased fatty acid catabolism. The second phase of hormesis could take place when AMPK activation was followed by COX-2 inhibition, yielding to accumulation of tFA and PUF. Another mechanism which could explain hormesis of metabolic pathways underlain by axis F2 is the response of pyruvate dehydrogenase to regulation of PDH kinase by ROS. Metabolite changes similar to those explaing F2 were reported in PDH kinase modulation by ROS. PDH blockade through ROS quenching by CUR at 24 h could account for Lac accumulation and fatty acid decrease. Hormetic reponses should contribute to apparently paradoxical responses to CUR. This is the reason why identifying biomarkers of the response to CUR is important. This study establishes that derivatives of glutathione metabolism and lipid metabolism are candidate biomarkers of the impact of CUR.