Elucidation of Biochemical Pathways Underlying VOCs Production in A549 Cells

Abstract

Cellular volatile organic compounds (VOCs) are unique compounds whose metabolic pathways remain enigmatic. To elucidate their metabolism, we investigated the VOCs of lung cancer A549 and 2 non-cancer lung cells (HLB; HBEpC). Neutral sugars and lactate in the medium were measured by colorimetric assay. VOCs were enriched by monotrap and profiled by GC-MS. To investigate the enzymes that change VOC metabolism in cells, we conducted ALDH activity assays and qPCR. ROS (reactive oxygen species) assays were conducted to assess oxidation stress. The colorimetric assay showed that especially A549 and HLB took up sugars from the medium and rapidly secreted lactate into the medium. The VOC profile (GC-MS) revealed a trans-2-hexenol increase, especially in A549 lung cancer cells. This is a novel lipid peroxidation product from animal cells. Based on the absolute quantification data, trans-2-hexenol increased in parallel with number of A549 cancer cells incubated. The qPCR data implies that ADH1c potentially plays an important role in the conversion into trans-2-hexenol.

The Volatilomic Footprints of Human HGC-27 and CLS-145 Gastric Cancer Cell Lines

“…The uptake of aldehydes is commonly observed in cultures of human cell lines both normal (Filipiak et al, 2010 ; Mochalski et al, 2015 ) and cancerous (Filipiak et al, 2008 ; Sponring et al, 2009 ; Mochalski et al, 2013b ). Studies reporting production of compounds from this chemical family by human cells are relatively sparse (Furuhashi et al, 2020 ). The consumption of aldehydes by human cells can be assigned to the expression of aldehyde dehydrogenases (ALDHs) oxidizing aldehydes into their corresponding carboxylic acids (Klyosov, 1996 ; Crabb et al, 2004 ).…”

“…2-ethylhexanol could also be the product of the oxidation of 2-ethyl-hexanal catalyzed by ADHs. Regarding other human cell lines, 2-ethylhexanol was shown to be liberated by A549 lung cancer cell line (Furuhashi et al, 2020 ).…”

“…HGC-27 cells were found to release toluene, the origin of which is unclear. The presence of toluene in human organism is commonly attributed to environmental exposure, or to smoking, but toluene was shown to be liberated by several human cell lines such as A549 lung cancer cells (Furuhashi et al, 2020 ) and human endothelial cells (HUVEC) (Mochalski et al, 2015 ).…”

The Genetic Basis of Tomato Aroma

“…In tomato fruit the latter is the most important for the production of volatiles, which occurs through two steps: (i) fatty acids are deoxygenated by means of lipoxygenases (LOX), which are classified as 13-LOX and 9-LOX and are leading respectively to 13-hydroperoxides and 9-hydroperoxides [67,108]; (ii) hydroperoxides are catabolized by means of hydroperoxide lyases (HPL), also classified as 13-HPL and 9-HPL, leading to an oxoacid and a volatile aldehyde. Volatile aldehydes can be converted into alcohols by means of alcohol dehydrogenases (ADH; [109][110][111][112][113][114]). According to the literature ( [68]), 13-LOX enzymes are mainly involved in the synthesis of (Z)-3-hexenal from linolenic acid and hexanal from linoleic acid.…”

“…Branched chain amino acid aminotransferases (BCATs) can be involved in the last step of BCAA anabolism and/or in the first step of BCAA catabolism depending on their subcellular localization (chloroplast or mitochondrion, respectively). Six BCAT genes were reported as candidate genes in Table 4, of which five (BCAT1, 2, 3, 4 and 7) have been functionally characterized [112,114]. Although BCAT2, 4 and 7 were located outside the QTL intervals, they were included in this review for completeness.…”