Abstract
BackgroundCrotonaldehyde, an alpha, beta-unsaturated aldehyde present in cigarette smoke, is an environmental pollutant and a product of lipid peroxidation. It also produces adverse effects to humans and is considered as a risk factor for various diseases. Heme oxygenase-1 (HO-1) plays important roles in protecting cells against oxidative stress as a prime cellular defense mechanism. However, HO-1 may be associated with cell proliferation and resistance to apoptosis in cancer cells. The aim of this study was to examine the effects of HO-1 induction on cell survival in crotonaldehyde-stimulated human hepatocellular carcinoma (HepG2) cells.MethodsTo investigate the signaling pathway involved in crotonaldehyde-induced HO-1 expression, we compared levels of inhibition efficiency of specific inhibitors and specific small interfering RNAs (siRNAs) of several kinases. The cell-cycle and cell death was measured by FACS and terminal dUTP nick-end labeling (TUNEL) staining.ResultsTreatment with crotonaldehyde caused a significant increase in nuclear translocation of NF-E2 related factor (Nrf2). Treatment with inhibitors of the protein kinase C-δ (PKC-δ) and p38 pathways resulted in obvious blockage of crotonaldehyde-induced HO-1 expression. Furthermore, treatment with HO-1 siRNA and the specific HO-1 inhibitor zinc-protoporphyrin produced an increase in the G0/G1 phase of the cell cycle in crotonaldehyde-stimulated HepG2 cells.ConclusionsTaken together, the results support an anti-apoptotic role for HO-1 in crotonaldehyde-stimulated human hepatocellular carcinoma cells and provide a mechanism by which induction of HO-1 expression via PKC-δ–p38 MAPK–Nrf2 pathway may promote tumor resistance to oxidative stress.
Highlights
Crotonaldehyde is a highly reactive alpha, beta-unsaturated aldehyde that occurs naturally in many foods and which is generated from lipid peroxidation [1], [2]
Treatment of HepG2 cells with crotonaldehyde produced a significant increase in the expression of Heme oxygenase-1 (HO-1) protein and mRNA in a dose-dependent manner (Figure 1A and 1C)
These results suggest that concentrations of crotonaldehyde below 50 mM are not toxic to HepG2 cells
Summary
Crotonaldehyde is a highly reactive alpha, beta-unsaturated aldehyde that occurs naturally in many foods and which is generated from lipid peroxidation [1], [2]. Cigarette smoke is generally considered to be the main source of human exposure to crotonaldehyde [3]. Several studies have revealed that crotonaldehyde reduces glutathione (GSH) levels and enhances the levels of intracellular reactive oxygen species (ROS), leading to a state of vulnerability in human airway cells [2], [11]. Crotonaldehyde, an alpha, beta-unsaturated aldehyde present in cigarette smoke, is an environmental pollutant and a product of lipid peroxidation. It produces adverse effects to humans and is considered as a risk factor for various diseases. The aim of this study was to examine the effects of HO-1 induction on cell survival in crotonaldehyde-stimulated human hepatocellular carcinoma (HepG2) cells
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
