<i>trans</i>-2-Pentenal, an Active Compound in Cigarette Smoke, Identified <i>via</i> Its Ability to Form Adducts with Glutathione

Abstract

α,β-Unsaturated carbonyl compounds readily form adducts with SH or NH 2 residues, which are nucleophilic agents, by Michael addition. Glutathione (GSH) is a tripeptide that contains an SH residue and functions as an antioxidant. We demonstrated previously that acrolein (ACR), crotonaldehyde (CA), and methyl vinyl ketone (MVK) are present in nicotine-and tar-removed cigarette smoke extract (CSE) and reacted with GSH in B16-BL6 mouse melanoma cells to form GSH-ACR, GSH-CA, and GSH-MVK adducts, suggesting a possible mechanism for CSE-induced cytotoxicity. In this study, we searched for novel α,β-unsaturated carbonyl compounds other than ACR, CA, and MVK. We selected candidate compounds in CSE based on accurate mass values generated using LC/MS analysis of products formed between CSE and GSH, and identified these using GC/MS analysis and library screening. As a result, we isolated trans-2-methyl-2-butenal, 2-methyl-2-cyclopenten-1-one, 3-methyl-2-cyclopenten-1-one, and furfural, which were poorly reactive with GSH and only very weakly inhibited growth of Colon-26 mouse carcinoma cells and BALB/3T3 clone A31 mouse normal cells. We also isolated 2-cyclopenten-1-one, trans-2-pentenal, 3-methyl-2-butenal and ethyl vinyl ketone, which were highly reactive with GSH and significantly inhibited the growth of both cell lines. Our data suggest that the reactivity of compounds in CSE with GSH may be positively correlated with the effect on inhibiting cell growth. Notably, trans-2-pentenal showed marked inhibition of carcinoma cells growth, whereas this compound exhibited little inhibitory effect on normal cells. trans-2-Pentenal may be a potent candidate or seed for antitumor agents.

The Combination of Cigarette Smoking and Alcohol Consumption Synergistically Increases Reactive Carbonyl Species in Human Male Plasma

“…The combination of smoking and alcohol drinking clearly showed significant synergistic effects on the plasma level of RCS, especially with regard to trans-2-alkenals (2-hexenal, 2-octenal, 2-nonenal, 2-decenal, and 2-undecenal), cis-4-alkenal (cis-4-decenal), alkadienals (2,4-hexadienal, 2,4-heptadienal, and 2,4-decadienal), alkanals (propanal, octanal, nonanal, decanal, undecanal, dodecanal, tridecanal, tetradecanal, and octadecanal), and an aromatic alkanal (benzaldehyde). Alkanals (≤C 10 ) and alkenals (≤C 6 ) have been detected in cigarette smoke (Table S1) [10][11][12][13], as they are contained in tobacco leaves and are also used as flavor additives for cigarettes. Thus, there is no surprise that higher levels of RCS were detected in the smoking/no-drinking group as compared to the no-smoking/no-drinking group in this study.…”

“…ROS cause alterations to nucleic acids and proteins, and generate reactive carbonyl species (RCS) via lipid peroxidation [9]. Various types of RCS have been detected in cigarette mainstream smoke, alcoholic beverages, and human biological samples (Table S1) [10][11][12][13][14][15][16][17][18].…”