J Nutr Health.  2018 Dec;51(6):498-506. 10.4163/jnh.2018.51.6.498.

Protective effect of lycopene against cytokine-induced β-cell apoptosis in INS-1 cells

Affiliations
  • 1Department of Food and Nutrition, Eulji University, Seongnam, Gyeonggi 13135, Korea. ysoh@eulji.ac.kr
  • 2Lee Gil Ya Cancer and Diabetes Institute, Department of Molecular Medicine, Gachon University, Incheon 21999, Korea.
  • 3College of Pharmacy, Gachon University, Incheon 21936, Korea.
  • 4Gachon Gil Medical Center, Incheon 21565, Korea.

Abstract

PURPOSE
Lycopene, a carotenoid with anti-oxidant properties, occurs naturally in tomatoes and pink grapefruit. Although the beneficial effects of lycopene on various disorders have been established, little attention has been paid to the possible anti-diabetic effects of lycopene focusing on β-cells. Therefore, this study investigated the potential of lycopene to protect β-cells against apoptosis induced by a cytokine mixture.
METHODS
For toxicity experiments, the cells were treated with 0.1 ~ 10 nM of lycopene, and the cell viability in INS-1 cells (a rat β-cell line) was measured using a MTT assay. To induce cytokine toxicity, the cells were treated with a cytokine mixture (20 ng/mL of TNFα+20 ng/mL of IL-1β) for 24 h, and the effects of lycopene (0.1 nM) on the cytokine toxicity were measured using the MTT assay. The expression levels of the apoptotic proteins were analyzed by Western blotting, and the level of intracellular reactive oxidative stress (ROS) was monitored using a DCFDA fluorescent probe. The intracellular ATP levels were determined using a luminescence kit, and mRNA expression of the genes coding for anti-oxidative stress response and mitochondrial function were analyzed by quantitative reverse-transcriptase PCR.
RESULTS
Exposure of INS-1 cells to 0.1 nM of lycopene increased the cell viability significantly, and protected the cells from cytokine-induced death. Lycopene upregulated the mRNA and protein expression of B-cell lymphoma-2 (Bcl-2) and reduced the expression of the Bcl-2 associated X (Bax) protein. Lycopene inhibited apoptotic signaling via a reduction of the ROS, and this effect correlated with the upregulation of anti-oxidative stress response genes, such as GCLC, NQO1, and HO-1. Lycopene increased the mRNA expression of mitochondrial function-related genes and increased the cellular ATP level.
CONCLUSION
These results suggest that lycopene reduces the level of oxidative stress and improves the mitochondrial function, contributing to the prevention of cytokine-induced β-cell apoptosis. Therefore, lycopene could potentially serve as a preventive and therapeutic agent for the treatment of type 2 diabetes.

Keyword

lycopene; β-cell; cytokine; apoptosis; type 2 diabetes

MeSH Terms

Adenosine Triphosphate
Animals
Apoptosis*
B-Lymphocytes
Blotting, Western
Cell Survival
Citrus paradisi
Clinical Coding
Luminescence
Lycopersicon esculentum
Oxidative Stress
Polymerase Chain Reaction
Rats
RNA, Messenger
Up-Regulation
Adenosine Triphosphate
RNA, Messenger
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