Hypoxia and lactate influence VOC production in A549 lung cancer cells

Takeshi Furuhashi; Yuki Matsumoto; Ryuga Ishii; Takehito Sugasawa; Shigenori Ota

doi:10.3389/fmolb.2023.1274298

Hypoxia and lactate influence VOC production in A549 lung cancer cells

Front Mol Biosci. 2023 Sep 21:10:1274298. doi: 10.3389/fmolb.2023.1274298. eCollection 2023.

Authors

Takeshi Furuhashi¹, Yuki Matsumoto¹, Ryuga Ishii¹, Takehito Sugasawa², Shigenori Ota³

Affiliations

¹ Anicom Specialty Medical Institute Inc., Tokyo, Japan.
² Laboratory of Clinical Examination/Sports Medicine, Division of Clinical Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan.
³ GL Science Inc., Saitama, Japan.

Abstract

Introduction: Cancer cells emit characteristic volatile organic compounds (VOCs), which are potentially generated from ROS-based lipid peroxidation of polyunsaturated fatty acids. The metabolism of such VOCs and their regulation remain to be fully investigated. In fact, the enzymes involved in the synthesis of these VOCs have not been described yet. Methods: In this study, we firstly conducted in vitro enzyme assays and demonstrated that recombinant alcohol dehydrogenase (ADH) converted Trans 2-hexenal into Trans 2-hexenol. The latter has previously been reported as a cancer VOC. To study VOC metabolism, 14 different culture conditions were compared in view of Trans 2-hexenol production. Results and discussion: The data indicate that hypoxia and the addition of lactate positively influenced Trans 2-hexenol production in A549 cancer cells. The RNAseq data suggested certain gene expressions in the VOC pathway and in lactate signaling, parallel to VOC production. This implies that hypoxia and lactate signaling with a VOC production can be characteristic for cancer in vitro.

Keywords: cancer metabolism; cellular VOC; hypoxia; lactic acid signaling; lipid peroxidation; lung cancer cell.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. Most of this research was financially supported by the Anicom Specialty Medical Institute Inc.