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Changes in Metabolic Profiles of Human Oral Cells by Benzylidene Ascorbates and Eugenol

1
Meikai University Research Institute of Odontology (M-RIO), 1-1 Keyakidai, Sakado, Saitama 350-0283, Japan
2
Institute for Advanced Biosciences, Keio University, Tsuruoka 997-0052, Japan
3
Health Promotion and Preemptive Medicine, Research and Development Center for Minimally Invasive Therapies, Tokyo Medical University, Shinjuku, Tokyo 160-0022, Japan
4
Research and Development Center for Precision Medicine, University of Tsukuba, Tukuba, Ibaraki 305-8550, Japan
5
Department of Microscope, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, Japan
6
Division of Oral Diagnosis and General Dentistry, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, Japan
7
Division of Anatomy, Meikai University School of Dentistry, 1-1 Keyakidai, Sakado, Saitama 350-0283, Japan
8
Ichijokai Hospital, 4-26-1 Kitakokubu, Ichikawa, Chiba 272-0836, Japan
*
Author to whom correspondence should be addressed.
Medicines 2018, 5(4), 116; https://doi.org/10.3390/medicines5040116
Received: 21 September 2018 / Revised: 23 October 2018 / Accepted: 24 October 2018 / Published: 31 October 2018
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Abstract

Background: Sodium-5,6-benzylidene-L-ascorbate (SBA), and its component units, benzaldehyde (BA) and sodium ascorbate (SA), are known to exert antitumor activity, while eugenol exerts anti-inflammatory activity. To narrow down their intracellular targets, metabolomic analysis was performed. Methods: Viable cell number was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. Fine cell structures were observed under transmission electron microscope. Cellular metabolites were extracted with methanol and subjected to capillary electrophoresis-mass spectrometry (CE-MS) for quantification of intracellular metabolites. Results: SBA was cleaved into BA and SA under acidic condition. Among these three compounds, BA showed the highest-tumor specificity in vitro against human oral squamous cell carcinoma (OSCC) cell line. BA did not induce the vacuolization in HSC-2 OSCC cells, and its cytotoxicity was not inhibited by catalase, in contrast to SBA and SA. Only BA suppressed the tricarboxylic acid (TCA) cycle at early stage of cytotoxicity induction. Eugenol more rapidly induced the vacuolization and suppressed the TCA cycle in three human normal oral cells (gingival fibroblast, periodontal ligament fibroblast, pulp cell). Neither BA nor eugenol affected the ATP utilization, further supporting that they do not induce apoptosis. Conclusions: The present study demonstrated for the first time that both BA and eugenol suppressed the TCA cycle in tumor cells and normal cells, respectively. It is crucial to design methodology that enhances the antitumor potential of BA and reduces the cytotoxicity of eugenol to allow for safe clinical application. View Full-Text
Keywords: metabolomics; oral cell; benzaldehyde; eugenol; inflammation; cytotoxicity metabolomics; oral cell; benzaldehyde; eugenol; inflammation; cytotoxicity
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Sakagami, H.; Sugimoto, M.; Kanda, Y.; Murakami, Y.; Amano, O.; Saitoh, J.; Kochi, A. Changes in Metabolic Profiles of Human Oral Cells by Benzylidene Ascorbates and Eugenol. Medicines 2018, 5, 116.

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