6 research outputs found
A common biological basis of obesity and nicotine addiction
J. Kaprio ja J. Tuomilehto työryhmien jäseniä (yht. 281).Peer reviewe
NMR Metabolomics Analysis of the Effects of 5‑Lipoxygenase Inhibitors on Metabolism in Glioblastomas
Changes across metabolic networks
are emerging as an integral part
of cancer development and progression. Increasing comprehension of
the importance of metabolic processes as well as metabolites in cancer
is stimulating exploration of novel, targeted treatment options. Arachidonic
acid (AA) is a major component of phospholipids. Through the cascade
catalyzed by cyclooxygenases and lipoxygenases, AA is also a precursor
to cellular signaling molecules as well as molecules associated with
a variety of diseases including cancer. 5-Lipoxygenase catalyzes the
transformation of AA into leukotrienes (LT), important mediators of
inflammation. High-throughput analysis of metabolic profiles was used
to investigate the response of glioblastoma cell lines to treatment
with 5-lipoxygenase inhibitors. Metabolic profiling of cells following
drug treatment provides valuable information about the response and
metabolic alterations induced by the drug action and give an indication
of both on-target and off-target effects of drugs. Four different
5-lipoxygenase inhibitors and antioxidants were tested including zileuton,
caffeic acid, and its analogues caffeic acid phenethyl ester and caffeic
acid cyclohexethyl ester. A NMR approach identified metabolic signatures
resulting from application of these compounds to glioblastoma cell
lines, and metabolic data were used to develop a better understanding
of the mode of action of these inhibitors