Effects of lycopene on number and function of human peripheral blood endothelial progenitor cells cultivated with high glucose

Abstract

BACKGROUND/OBJECTIVESThe objectives of this study were to investigate the effects of lycopene on the migration, adhesion, tube formation capacity, and p38 mitogen-activated protein kinase (p38 MAPK) activity of endothelial progenitor cells (EPCs) cultivated with high glucose (HG) and as well as explore the mechanism behind the protective effects of lycopene on peripheral blood EPCs.MATERIALS/METHODSMononuclear cells were isolated from human peripheral blood by Ficoll density gradient centrifugation. EPCs were identified after induction of cellular differentiation. Third generation EPCs were incubated with HG (33 mmol/L) or 10, 30, and 50 µg/mL of lycopene plus HG. MTT assay and flow cytometry were performed to assess proliferation and apoptosis of EPCs. EPC migration was assessed by MTT assay with a modified boyden chamber. Adhesion assay was performed by replating EPCs on fibronectin-coated dishes, after which adherent cells were counted. In vitro vasculogenesis activity was assayed by Madrigal network formation assay. Western blotting was performed to analyze protein expression of both phosphorylated and non-phosphorylated p38 MAPK.RESULTSThe proliferation, migration, adhesion, and in vitro vasculogenesis capacity of EPCs treated with 10, 30, and 50 µg/mL of lycopene plus HG were all significantly higher comapred to the HG group (P < 0.05). Rates of apoptosis were also significantly lower than that of the HG group. Moreover, lycopene blocked phosphorylation of p38 MAPK in EPCs (P < 0.05). To confirm the causal relationship between MAPK inhibition and the protective effects of lycopene against HG-induced cellular injury, we treated cells with SB203580, a phosphorylation inhibitor. The inhibitor significantly inhibited HG-induced EPC injury.CONCLUSIONSLycopene promotes proliferation, migration, adhesion, and in vitro vasculogenesis capacity as well as reduces apoptosis of EPCs. Further, the underlying molecular mechanism of the protective effects of lycopene against HG-induced EPC injury may involve the p38 MAPK signal transduction pathway. Specifically, lycopene was shown to inhibit HG-induced EPC injury by inhibiting p38 MAPKs.

Lycopene: A Potent Antioxidant for the Amelioration of Type II Diabetes Mellitus

“…Moreover, it has been shown that vascular endothelial dysfunction and the number of endothelial progenitor cells (EPCs) are important risk factors for the development of vascular complications in T2DM. Zeng et al [ 108 ] reported that lower cell proliferation, migration, adhesion, and in vitro vasculogenesis capacity, as well as increased EPC’s apoptosis, were observed in the high glucose rats group. Lycopene treatment inhibits high glucose-induced EPC injury by inhibiting ROS generation and downregulating phosphorylation of p38 mitogen-activated protein kinases (p38 MAPK).…”

Lycopene prevents cell death in NRK‐52E cells by inhibition of high glucose‐activated DNA damage and apoptotic, autophagic, and necrotic pathways

“…[ 37–44 ] It was also stated that lycopene was effective in regulating blood sugar, insulin, and insulin intolerance by inhibiting STAT3 signaling. [ 45,46 ] There are also in vitro studies on lycopene, but they are mostly focused on cancer cell lines.…”

“…intolerance by inhibiting STAT3 signaling. [45,46] There are also in vitro studies on lycopene, but they are mostly focused on cancer cell lines.…”

Beneficial Effect of Lycopene on Diabetes Mellitus and its Possible Mechanism: A Review

“…35 Lycopene has a good antioxidant activity, especially against oxygenderived radicals and has the highest singlet oxygen quenching capability among all carotenoids in biological systems. 18,22 The large number of conjugated double bonds in lycopene makes it a potent antioxidant because the delocalization of π electrons that occurs along the double bond allows the neutralization reaction of molecules containing unpaired electrons. 19,35 The radical neutralization reaction of lycopene can occur in various ways, including adding radicals to the polyene chain, electron transfer from lycopene to radicals, or eliminating hydrogen atoms from lycopene.…”

“…Many studies have shown that lycopene shows potential beneficial effects in cancer and lifelong diseases, such as cardiovascular, neurodegenerative, and metabolic diseases which includes diabetes. [20][21][22] In vitro and in vivo studies show that lycopene has potential in diabetes therapy and prevention of disease progression associated with diabetes complications but have not yet explained its molecular mechanism in detail. Therefore, this literature review was made to summarize the results of studies (see Tables 1-4) related to the beneficial effect of lycopene in DM in the last decade and highlight several important molecular pathways (see Figure 1) involved such as oxidative stress, inflammation (nuclear factor-kappa B [NF-κB] pathway), insulin signaling (phosphatidylinositol 3-kinase [PI3K]/AKT pathway), apoptosis, and autophagy.…”