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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 the MPP+-induced ROS production in SH-SY5Y cells. Intracellular ROS production was measured after treatment cells with 10 μM alpha-mangostin (α-M), 1000 μM MPP+, or the combination of α-M and MPP+ for 6 hours. Flow cytometric analysis of ROS production is presented as the mean fluorescence intensity (MFI), as assessed by incubation with DHE (a) and DHR123 fluorescence dye (b). Data are expressed as mean ± SEM (n = 3), compared to untreated cells.  ∗P < 0.001.
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fig6: Effect of alpha-mangostin on the MPP+-induced ROS production in SH-SY5Y cells. Intracellular ROS production was measured after treatment cells with 10 μM alpha-mangostin (α-M), 1000 μM MPP+, or the combination of α-M and MPP+ for 6 hours. Flow cytometric analysis of ROS production is presented as the mean fluorescence intensity (MFI), as assessed by incubation with DHE (a) and DHR123 fluorescence dye (b). Data are expressed as mean ± SEM (n = 3), compared to untreated cells.  ∗P < 0.001.

Mentions: To evaluate whether ROS play an important role in the attenuation effect of alpha-mangostin on MPP+-induced apoptosis in SH-SY5Y cells, cells were exposed to 1000 μm MPP+ and 10 μm alpha-mangostin plus 1000 um MPP+ for 6 hours, and intracellular ROS production was assessed as DHE and DHR123 fluorescence using flow cytometry. The result shows that cotreatment with 10 μm alpha-mangostin in the presence of 1000 μm MPP+ significantly decreased intracellular ROS levels as measured by the mean fluorescence intensity (MFI) of DHE (P < 0.001; Figure 6(a)) and DHR123 (P < 0.001; Figure 6(b)), compared to MPP+ treatment alone.


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 the MPP+-induced ROS production in SH-SY5Y cells. Intracellular ROS production was measured after treatment cells with 10 μM alpha-mangostin (α-M), 1000 μM MPP+, or the combination of α-M and MPP+ for 6 hours. Flow cytometric analysis of ROS production is presented as the mean fluorescence intensity (MFI), as assessed by incubation with DHE (a) and DHR123 fluorescence dye (b). Data are expressed as mean ± SEM (n = 3), compared to untreated cells.  ∗P < 0.001.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC4556078&req=5

fig6: Effect of alpha-mangostin on the MPP+-induced ROS production in SH-SY5Y cells. Intracellular ROS production was measured after treatment cells with 10 μM alpha-mangostin (α-M), 1000 μM MPP+, or the combination of α-M and MPP+ for 6 hours. Flow cytometric analysis of ROS production is presented as the mean fluorescence intensity (MFI), as assessed by incubation with DHE (a) and DHR123 fluorescence dye (b). Data are expressed as mean ± SEM (n = 3), compared to untreated cells.  ∗P < 0.001.
Mentions: To evaluate whether ROS play an important role in the attenuation effect of alpha-mangostin on MPP+-induced apoptosis in SH-SY5Y cells, cells were exposed to 1000 μm MPP+ and 10 μm alpha-mangostin plus 1000 um MPP+ for 6 hours, and intracellular ROS production was assessed as DHE and DHR123 fluorescence using flow cytometry. The result shows that cotreatment with 10 μm alpha-mangostin in the presence of 1000 μm MPP+ significantly decreased intracellular ROS levels as measured by the mean fluorescence intensity (MFI) of DHE (P < 0.001; Figure 6(a)) and DHR123 (P < 0.001; Figure 6(b)), compared to MPP+ treatment alone.

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