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Neuroprotective Effects of Alpha-Mangostin on MPP(+)-Induced Apoptotic Cell Death in Neuroblastoma SH-SY5Y Cells.

Janhom P, Dharmasaroja P - J Toxicol (2015)

Bottom Line: Alpha-mangostin reduced ROS formation induced by MPP(+).The cotreated cells showed a significant decrease in activated caspase-3 compared with MPP(+) treatment alone.Our data suggest that cytoprotection of alpha-mangostin against MPP(+)-induced apoptosis may be associated with the reduction of ROS production, modulating the balance of pro- and antiapoptotic genes, and suppression of caspase-3 activation.

View Article: PubMed Central - PubMed

Affiliation: Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.

ABSTRACT
In vitro studies have shown that extracts from mangosteen (Garcinia mangostana Linn.) act as antioxidants and cytoprotective agents against oxidative damage. The protective effect of alpha-mangostin, the major xanthone found in the pericarp of the mangosteen, in cellular models of Parkinson's disease (PD), has not been investigated. This study aims to investigate whether alpha-mangostin could protect SH-SY5Y neuroblastoma cells from MPP(+)-induced apoptosis. The effects of alpha-mangostin on MPP(+)-induced cell death were evaluated with a cell viability assay, staining for nuclear DNA morphology, flow cytometry for apoptotic cells and reactive oxygen species (ROS) production, quantitative real-time PCR for the expression of p53, Bax, and Bcl-2, and western blot analysis for cleaved caspase-3. Concomitant treatment with alpha-mangostin attenuated the effect of MPP(+) on cell viability and apoptotic cell death. Alpha-mangostin reduced ROS formation induced by MPP(+). Bax/Bcl-2 expression ratio and expression of p53 were significantly lower in cells cocultured with alpha-mangostin and MPP(+). The cotreated cells showed a significant decrease in activated caspase-3 compared with MPP(+) treatment alone. Our data suggest that cytoprotection of alpha-mangostin against MPP(+)-induced apoptosis may be associated with the reduction of ROS production, modulating the balance of pro- and antiapoptotic genes, and suppression of caspase-3 activation.

No MeSH data available.


Related in: MedlinePlus

Effect of alpha-mangostin on cleaved caspase-3 protein expression in MPP+-treated SH-SY5Y cells. Cells were treated with 10 μM alpha-mangostin (α-M), 1000 μM MPP+, or the combination of α-M and MPP+ for 24 hours. Cleaved caspase-3 was detected with Western blotting. The density of bands was analyzed in comparison with that of β-actin. Data are expressed as mean ± SEM (n = 3).  ∗P < 0.01.
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fig8: Effect of alpha-mangostin on cleaved caspase-3 protein expression in MPP+-treated SH-SY5Y cells. Cells were treated with 10 μM alpha-mangostin (α-M), 1000 μM MPP+, or the combination of α-M and MPP+ for 24 hours. Cleaved caspase-3 was detected with Western blotting. The density of bands was analyzed in comparison with that of β-actin. Data are expressed as mean ± SEM (n = 3).  ∗P < 0.01.

Mentions: To investigate the effect of alpha-mangostin on the caspase-3 protein, a critical executioner of apoptosis, a Western blot analysis was conducted. Activation of caspase-3 requires cleavage of the protein at Asp175 into the activated p17 and p19 fragments. After a 24-hour treatment of SH-SY5Y cells with 1000 μm MPP+, a significant increase in activated caspase-3 protein was detected compared to the level in control cells (Figure 8). When SH-SY5Y cells were exposed to 10 μm alpha-mangostin in the presence of 1000 μm MPP+, the cotreated cells showed a significant decrease in activated caspase-3 compared to the MPP+ treatment alone (P < 0.001).


Neuroprotective Effects of Alpha-Mangostin on MPP(+)-Induced Apoptotic Cell Death in Neuroblastoma SH-SY5Y Cells.

Janhom P, Dharmasaroja P - J Toxicol (2015)

Effect of alpha-mangostin on cleaved caspase-3 protein expression in MPP+-treated SH-SY5Y cells. Cells were treated with 10 μM alpha-mangostin (α-M), 1000 μM MPP+, or the combination of α-M and MPP+ for 24 hours. Cleaved caspase-3 was detected with Western blotting. The density of bands was analyzed in comparison with that of β-actin. Data are expressed as mean ± SEM (n = 3).  ∗P < 0.01.
© Copyright Policy - open-access
Related In: Results  -  Collection

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fig8: Effect of alpha-mangostin on cleaved caspase-3 protein expression in MPP+-treated SH-SY5Y cells. Cells were treated with 10 μM alpha-mangostin (α-M), 1000 μM MPP+, or the combination of α-M and MPP+ for 24 hours. Cleaved caspase-3 was detected with Western blotting. The density of bands was analyzed in comparison with that of β-actin. Data are expressed as mean ± SEM (n = 3).  ∗P < 0.01.
Mentions: To investigate the effect of alpha-mangostin on the caspase-3 protein, a critical executioner of apoptosis, a Western blot analysis was conducted. Activation of caspase-3 requires cleavage of the protein at Asp175 into the activated p17 and p19 fragments. After a 24-hour treatment of SH-SY5Y cells with 1000 μm MPP+, a significant increase in activated caspase-3 protein was detected compared to the level in control cells (Figure 8). When SH-SY5Y cells were exposed to 10 μm alpha-mangostin in the presence of 1000 μm MPP+, the cotreated cells showed a significant decrease in activated caspase-3 compared to the MPP+ treatment alone (P < 0.001).

Bottom Line: Alpha-mangostin reduced ROS formation induced by MPP(+).The cotreated cells showed a significant decrease in activated caspase-3 compared with MPP(+) treatment alone.Our data suggest that cytoprotection of alpha-mangostin against MPP(+)-induced apoptosis may be associated with the reduction of ROS production, modulating the balance of pro- and antiapoptotic genes, and suppression of caspase-3 activation.

View Article: PubMed Central - PubMed

Affiliation: Toxicology Graduate Program, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.

ABSTRACT
In vitro studies have shown that extracts from mangosteen (Garcinia mangostana Linn.) act as antioxidants and cytoprotective agents against oxidative damage. The protective effect of alpha-mangostin, the major xanthone found in the pericarp of the mangosteen, in cellular models of Parkinson's disease (PD), has not been investigated. This study aims to investigate whether alpha-mangostin could protect SH-SY5Y neuroblastoma cells from MPP(+)-induced apoptosis. The effects of alpha-mangostin on MPP(+)-induced cell death were evaluated with a cell viability assay, staining for nuclear DNA morphology, flow cytometry for apoptotic cells and reactive oxygen species (ROS) production, quantitative real-time PCR for the expression of p53, Bax, and Bcl-2, and western blot analysis for cleaved caspase-3. Concomitant treatment with alpha-mangostin attenuated the effect of MPP(+) on cell viability and apoptotic cell death. Alpha-mangostin reduced ROS formation induced by MPP(+). Bax/Bcl-2 expression ratio and expression of p53 were significantly lower in cells cocultured with alpha-mangostin and MPP(+). The cotreated cells showed a significant decrease in activated caspase-3 compared with MPP(+) treatment alone. Our data suggest that cytoprotection of alpha-mangostin against MPP(+)-induced apoptosis may be associated with the reduction of ROS production, modulating the balance of pro- and antiapoptotic genes, and suppression of caspase-3 activation.

No MeSH data available.


Related in: MedlinePlus