Background & Aims Oxidative stress (OS) plays an important role in neurodegenerative diseases such as Alzheimer’s disease (AD). Lycopene is a pigment with potent antioxidant and anti-tumor effects. However, its potential role in central nervous system is not well-defined. The aim of this study was to investigate the effect of lycopene on the cell model of AD and determine its underlying mechanisms. Methods M146L cell is a double-transfected (human APP gene and presenlin-1 gene) Chinese hamster ovary (CHO) cell line that overexpresses β -amyloid (Aβ) and is an ideal cell model for AD. We treated cells with lycopene, and observed the effect of lycopene on M146L cells. Results Oxidative stress and apoptosis in M146L cells were significantly higher than those in CHO cells, suggesting that Aβ induced OS and apoptosis. Lycopene alleviated OS and apoptosis, activated the PI3K/Akt/Nrf2 signaling pathway, upregulated antioxidant and antiapoptotic proteins and downregulated proapoptotic proteins. Additionally, lycopene inhibited β -secretase (BACE) activity in M146L cells. These results suggest that lycopene inhibits BACE activity and protects M146L cells from oxidative stress and apoptosis by activating the PI3K/Akt/Nrf2 pathway. Conclusion Lycopene possibly prevents Aβ-induced damage by activating the PI3K/Akt/Nrf2 signaling pathway and reducing the expression of BACE in M146L cells.
Gliomas are the most common neoplasm of the human central nervous system. Glioblastoma multiforme (GBM) is one of the most serious types of gliomas. Although considerable progress has been made in the development of cancer therapeutic agents, several antineoplastic drugs fail to penetrate the blood-brain barrier (BBB), resulting in a low survival rate of glioma patients. Recent studies have revealed that the traditional Chinese medicine Buxus microphylla contains the main active component Cyclovirobuxine D (CVB-D), which can cross the BBB with a novel delivery system. However, it remains unclear whether CVB-D exerts anticancer effects against GBM and low-grade glioma (LGG). The aim of the present study was to explore the feasibility of CVB-D as a new effective agent in the treatment of GBM and LGG. The ability of CVB-D to inhibit GBM and LGG cell proliferation was detected by CCK8 assay. Flow cytometry was used to detect cell cycle progression and apoptosis induction by Annexin V-FITC/PI assay. The expression levels of the apoptosis-associated proteins, namely cleaved caspase-3 and Bax/Bcl-2, were detected by western blot analysis. The mitochondrial membrane potential (ΔΨm) was detected by Rh123 dyed fluorescence micrograph. Hoechst staining was used to observe the morphological characteristics of the apoptotic cells. The scratch test was used to evaluate the migration of GBM and LGG cells. The results indicated that CVB-D reduced cell viability of T98G and Hs683 cells. Flow cytometry demonstrated that CVB-D-treated cells were arrested at the S phase of their cell cycle. The expression levels of the apoptosis-associated proteins were increased in CVB-D-treated cells. Rh123 and Hoechst staining indicated morphological changes and mitochondrial membrane potential changes of the cells undergoing apoptosis. The data confirmed that CVB-D inhibited cell proliferation by arresting the cell cycle of GBM and LLG cells and that it promoted the induction of cell apoptosis by altering the mitochondrial membrane potential. The findings of the present study indicate the potential value of CVB-D in the treatment of glioma.
Lycopene is a pigment derived from tomatoes and other red fruits, and has potent antioxidant and antitumor effects. However, its potential role in alleviating oxidative damage in neuronal cells is not well defined. In this study, we investigated the effects of lycopene on H 2 O 2-induced damage in neuroblastoma cells, as well as the underlying mechanisms. Exposure to H 2 O 2 markedly decreased the viability of SH-SY5Y cells and increased LDH release, both of which were reversed by lycopene pretreatment. Lycopene also ameliorated H 2 O 2-induced damage and reduced the expression of apoptotic markers, such as Bcl-2, Bax, and cleaved caspase 3. In addition, the H 2 O 2-induced oxidative markers, including MDA, 8-OHdG, and protein carbonyls, were also downregulated by lycopene. Exogenous H 2 O 2 activated the GRP78/PERK/eIF2α signaling pathway, which was inhibited by pretreatment with lycopene. Finally, lycopene significantly ameliorated ER stress-induced activation and nuclear translocation of CHOP. Overexpression of CHOP markedly reversed the antiapoptotic effects of lycopene, indicating that it is essential for the latter's protective effects. Taken together, lycopene protects neuroblastoma cells from oxidative stress and ER stress-induced damage by inhibiting the PERK-CHOP signaling pathway, which is a potential therapeutic target in neurodegenerative diseases.
Alzheimer’s disease (AD) is a neurodegenerative condition associated with oxidative stress and neuroinflammation. Lycopene has previously been shown to ameliorate neuroinflammation and exert protection against oxidative damage in neuroblastoma cells. The role of this compound in reversing cognitive dysfunction in AD has yet to be determined. The present study investigates the role of lycopene in AD with an in vitro Aβ1-42-induced cell cytotoxicity model as well as the in vivo APP/PS1 mouse model. The activation of Nrf2 signal pathway was assessed using western blot and RT-PCR. MDA, 8-OHdG, ROS, SOD, GHS and GSSG measurements were carried out using the specialized assay kits. The Morris water maze was used to examine qualitative assessment of memory and spatial learning. Immunofluorescence was used to visualize astrocytes and microglia activation as well as brain β-amyloid (Aβ) deposition. The NeuN positive cells were detected by immunofluorescence and western blot. Levels of cerebral cytokines were quantified using RT-PCR. Lycopene ameliorates oxidative damage in the Aβ1-42-triggered cell cytotoxicity model via Nrf2-ARE signal pathway activation, which is regulated by AKT-GSK3β pathway. In addition, lycopene improves the cognitive impairment and reduces the Aβ deposition. Mechanistically, lycopene attenuates neuron loss, decreases chronic inflammation and activates cerebral Nrf2-ARE signaling pathway in APP/PS1 mice. The results suggest that lycopene alleviates oxidative stress via AKT- Nrf2-ARE pathway. And early administration of lycopene improves cognitive deficits by reducing Aβ deposition, neuronal loss and decreasing the degree of chronic inflammation.
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