RT Journal Article SR Electronic T1 Changes of Metabolic Profiles in an Oral Squamous Cell Carcinoma Cell Line Induced by Eugenol JF In Vivo JO In Vivo FD International Institute of Anticancer Research SP 233 OP 243 VO 27 IS 2 A1 TEHO KOH A1 YUKIO MURAKAMI A1 SHOJI TANAKA A1 MAMORU MACHINO A1 HIROMI ONUMA A1 MIKU KANEKO A1 MASAHIRO SUGIMOTO A1 TOMOYOSHI SOGA A1 MASARU TOMITA A1 HIROSHI SAKAGAMI YR 2013 UL http://iv.iiarjournals.org/content/27/2/233.abstract AB Background: We have recently reported that eugenol exerted indiscriminate cytotoxicity towards normal oral cells and oral squamous cell carcinoma (OSCC) cell lines without induction of apoptosis markers. In order to investigate the underlying mechanisms of cytotoxicity induction, we investigated the effect of short-term treatment with eugenol on the metabolic profiles of a human OSCC cell line (HSC-2). Materials and Methods: The viable cell number was determined by direct cell counting with a hemocytometer after trypsinization. After washing with 5% D-mannitol solution (found to retain the highest amounts of intracellular metabolites among several washing conditions), cellular metabolites were extracted with methanol with internal markers and then subjected to metabolomic analysis. Results: Cytotoxic concentrations of eugenol induced the reduction of ATP utilization (assessed by a significant reduction of the AMP/ATP and ADP/ATP ratio), of oxidative stress (assessed by the increase in oxidized form of glutathione, cysteine-glutathione disulfide and methionine sulfoxide), and an increase in the polyamines and glycolytic metabolites. Conclusion: The metabolic changes observed in this study suggest the induction of non-apoptotic cell death by eugenol.