4-Hydroxynonenal modulation of p53 family gene expression in the SK-N-BE neuroblastoma cell line
Related Experiment Video
Updated: Aug 20, 2026

Yeast As a Chassis for Developing Functional Assays to Study Human P53
Published on: August 4, 2019
Stefano Laurora1, Elena Tamagno, Federica Briatore
1Department of Experimental Medicine and Oncology, Section of General Pathology, University of Turin, Corso Raffaello 30, 10125 Turin, Italy.
Abstract:
4-Hydroxynonenal (HNE), a product of lipid peroxidation, inhibits proliferation of several tumor cells. The p53 tumor suppressor protein plays a critical role in cell cycle control, by inducing p21 expression, and in apoptosis, by inducing bax expression. Recently, two other proteins with many p53-like properties, TAp73 (p73) and TAp63 (p63), have been discovered. SK-N-BE human neuroblastoma cells express the three p53 family proteins and can be used for the study of their induction. We investigated HNE action in the control of proliferation, differentiation, and apoptosis in SK-N-BE cells and the HNE effect on the expression of p53, p63, p73, p21, bax, and G1 cyclins. Retinoic acid (RA) was used as a positive control. HNE inhibited cell proliferation without inducing differentiation; it decreased S-phase cells and increased the number of apoptotic cells. RA reduced the proportion of S-phase cells and did not induce apoptosis. HNE increased p53, p73, p63, p21, and bax expression at different time points. HNE reduced cyclin D2 expression and the phosphorylation of pRb protein. Our results demonstrated that HNE inhibits SK-N-BE cell proliferation by increasing the expression of p53 family proteins and p53 target proteins which modulate cell cycle progression and apoptosis.
Insights
4-Hydroxynonenal (HNE), a lipid peroxidation product, inhibits neuroblastoma cell proliferation by increasing p53 family proteins and apoptosis-related gene expression. This study reveals HNE
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- 4-Hydroxynonenal (HNE) is a cytotoxic product of lipid peroxidation.
- The p53 tumor suppressor protein family, including p53, p63, and p73, regulates cell cycle and apoptosis.
- SK-N-BE human neuroblastoma cells express all three p53 family members.
Purpose of the Study:
- To investigate the effects of HNE on proliferation, differentiation, and apoptosis in SK-N-BE cells.
- To determine the impact of HNE on the expression of p53 family proteins (p53, p63, p73) and their target genes (p21, bax).
- To elucidate the role of HNE in modulating cell cycle regulators like G1 cyclins and pRb phosphorylation.
Main Methods:
- Treatment of SK-N-BE neuroblastoma cells with HNE and retinoic acid (RA) as a control.
- Analysis of cell proliferation, cell cycle phase distribution (S-phase), differentiation markers, and apoptosis.
- Quantitative assessment of p53, p63, p73, p21, and bax protein and gene expression.
- Evaluation of cyclin D2 expression and pRb protein phosphorylation.
Main Results:
- HNE inhibited cell proliferation and decreased the proportion of S-phase cells without inducing differentiation.
- HNE significantly increased the number of apoptotic cells.
- HNE upregulated the expression of p53, p73, p63, p21, and bax at various time points.
- HNE downregulated cyclin D2 expression and reduced pRb phosphorylation.
Conclusions:
- HNE effectively inhibits neuroblastoma cell proliferation.
- The antiproliferative effect of HNE is mediated through the induction of p53 family proteins and their downstream targets involved in cell cycle arrest and apoptosis.
- HNE represents a potential therapeutic agent targeting cell cycle progression and inducing apoptosis in neuroblastoma.
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