Biomol Ther.  2015 Nov;23(6):517-524. 10.4062/biomolther.2015.085.

Pretreatment with Lycopene Attenuates Oxidative Stress-Induced Apoptosis in Human Mesenchymal Stem Cells

• Kim JY
• Lee JS
• Han YS
• Lee JH
• Bae I
• Yoon YM
• Kwon SM
• Lee SH

• KMID: 2380302
• DOI: http://doi.org/10.4062/biomolther.2015.085

Abstract

Human mesenchymal stem cells (MSCs) have been used in cell-based therapy to promote revascularization after peripheral or myocardial ischemia. High levels of reactive oxygen species (ROS) are involved in the senescence and apoptosis of MSCs, causing defective neovascularization. Here, we examined the effect of the natural antioxidant lycopene on oxidative stress-induced apoptosis in MSCs. Although H2O2 (200 muM) increased intracellular ROS levels in human MSCs, lycopene (10 muM) pretreatment suppressed H2O2-induced ROS generation and increased survival. H2O2-induced ROS increased the levels of phosphorylated p38 mitogen activated protein kinase (MAPK), Jun-N-terminal kinase (JNK), ataxia telangiectasia mutated (ATM), and p53, which were inhibited by lycopene pretreatment. Furthermore, lycopene pretreatment decreased the expression of cleaved poly (ADP ribose) polymerase-1 (PARP-1) and caspase-3 and increased the expression of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax), which were induced by H2O2 treatment. Moreover, lycopene significantly increased manganese superoxide dismutase (MnSOD) expression and decreased cellular ROS levels via the PI3K-Akt pathway. Our findings show that lycopene pretreatment prevents ischemic injury by suppressing apoptosis-associated signal pathway and enhancing anti-oxidant protein, suggesting that lycopene could be developed as a beneficial broad-spectrum agent for the successful MSC transplantation in ischemic diseases.

Keyword

Lycopene; MSC; Oxidative stress; Apoptosis; Anti-oxidant reagent

MeSH Terms

Aging
Apoptosis*
Ataxia Telangiectasia
bcl-2-Associated X Protein
Caspase 3
Humans*
Lymphoma, B-Cell
Mesenchymal Stromal Cells*
Myocardial Ischemia
Oxidative Stress
Phosphotransferases
Protein Kinases
Reactive Oxygen Species
Signal Transduction
Superoxide Dismutase
Caspase 3
Phosphotransferases
Protein Kinases
Reactive Oxygen Species
Superoxide Dismutase
bcl-2-Associated X Protein