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Lycopene Inhibits Metastasis of Human Liver Adenocarcinoma SK-Hep-1 Cells by Downregulation of NADPH Oxidase 4
Bo-Yi Jhou1, Tuzz-Ying Song2, Inn Lee3
1Department of Food Science and Biotechnology, National Chung Hsing University , Taichung, Taiwan.
Abstract:
NADPH oxidase 4 (NOX4), with the sole function to produce reactive oxygen species (ROS), can be a molecular target for disrupting cancer metastasis. Several studies have indicated that lycopene exhibited anti-metastatic actions in vitro and in vivo. However, the role of NOX4 in the anti-metastatic action of lycopene remains unknown. Herein, we first confirmed the anti-metastatic effect of lycopene (0.1-5 μM) on human liver adenocarcinoma SK-Hep-1 cells. We showed that lycopene significantly inhibited NOX4 protein expression, with the strongest inhibition of 64.3 ± 10.2% (P < 0.05) at 2.5 μM lycopene. Lycopene also significantly inhibited NOX4 mRNA expression, NOX activity, and intracellular ROS levels in SK-Hep-1 cells. We then determined the effects of lycopene on transforming growth factor β (TGF-β)-induced metastasis. We found that TGF-β (5 ng/mL) significantly increased migration, invasion, and adhesion activity, the intracellular ROS level, matrix metalloproteinase 9 (MMP-9) and MMP-2 activities, the level of NOX4 protein expression, and NOX activity. All these TGF-β-induced effects were antagonized by the incubation of SK-Hep-1 cells with lycopene (2.5 μM). Using transient transfection of siRNA against NOX4, we found that the downregulation of NOX4 could mimic lycopene by inhibiting cell migration and the activities of MMP-9 and MMP-2 during the incubation with or without TGF-β on SK-Hep-1 cells. The results demonstrate that the downregulation of NOX4 plays a crucial role in the anti-metastatic action of lycopene in SK-Hep-1 cells.
Insights
Lycopene inhibits cancer metastasis by reducing NADPH oxidase 4 (NOX4) and reactive oxygen species (ROS) production. Downregulating NOX4 mimics lycopene
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- NADPH oxidase 4 (NOX4) produces reactive oxygen species (ROS) and is a potential target for anti-cancer metastasis strategies.
- Lycopene has demonstrated anti-metastatic properties in various studies.
- The specific role of NOX4 in lycopene's anti-metastatic effects is not well understood.
Purpose of the Study:
- To investigate the role of NOX4 in the anti-metastatic action of lycopene in human liver adenocarcinoma cells (SK-Hep-1).
- To determine if lycopene affects NOX4 expression, activity, and ROS production.
- To examine lycopene's impact on transforming growth factor β (TGF-β)-induced metastatic processes.
Main Methods:
- Treatment of SK-Hep-1 cells with varying concentrations of lycopene.
- Assessment of NOX4 protein and mRNA expression, NOX activity, and intracellular ROS levels.
- Induction of metastasis using TGF-β and evaluation of cell migration, invasion, and adhesion.
- Utilizing siRNA to downregulate NOX4 expression and observe its effects on metastasis and enzyme activities.
Main Results:
- Lycopene significantly inhibited NOX4 protein and mRNA expression, NOX activity, and intracellular ROS levels in SK-Hep-1 cells.
- Lycopene (2.5 μM) antagonized TGF-β-induced increases in cell migration, invasion, adhesion, ROS levels, and matrix metalloproteinase (MMP-9 and MMP-2) activities.
- Downregulation of NOX4 using siRNA mimicked lycopene's inhibitory effects on cell migration and MMP activities, both with and without TGF-β stimulation.
Conclusions:
- NOX4 downregulation is a critical mechanism underlying the anti-metastatic effects of lycopene in liver adenocarcinoma cells.
- Lycopene's ability to inhibit NOX4 and subsequent ROS production contributes to its anti-metastatic potential.
- Targeting NOX4 presents a promising therapeutic strategy for combating cancer metastasis.
