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Pterostilbene exerts antitumor activity via the Notch1 signaling pathway in human lung adenocarcinoma cells.

Yang Y, Yan X, Duan W, Yan J, Yi W, Liang Z, Wang N, Li Y, Chen W, Yu S, Jin Z, Yi D - PLoS ONE (2013)

Bottom Line: PTE treatment resulted in a dose- and time-dependent decrease in the viability of A549 cells.DAPT (a gamma secretase inhibitor) and Notch1 siRNA prevented the induction of NICD and Hes1 activation by PTE treatment and sensitized the cells to PTE treatment.The down-regulation of Notch signaling also prevented the activation of pro-survival pathways (most notably the PI3K/Akt pathway) after PTE treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an City, China.

ABSTRACT
Although pterostilbene (PTE) has been shown to have potent antitumor activities against various cancer types, the molecular mechanisms of these activities remain unclear. In this study, we investigated the antitumor activity of PTE against human lung adenocarcinoma in vitro and in vivo and explored the role of the Notch1 signaling pathway in this process. PTE treatment resulted in a dose- and time-dependent decrease in the viability of A549 cells. Additionally, PTE exhibited strong antitumor activity, as evidenced not only by a reduced mitochondrial membrane potential (MMP) and a decreased intracellular glutathione content but also by increases in the apoptotic index and the level of reactive oxygen species (ROS). Furthermore, PTE treatment induced the activation of the Notch1 Intracellular Domain (NICD) protein and activated Hes1. DAPT (a gamma secretase inhibitor) and Notch1 siRNA prevented the induction of NICD and Hes1 activation by PTE treatment and sensitized the cells to PTE treatment. The down-regulation of Notch signaling also prevented the activation of pro-survival pathways (most notably the PI3K/Akt pathway) after PTE treatment. In summary, lung adenocarcinoma cells may enhance Notch1 activation as a protective mechanism in response to PTE treatment. Combining a gamma secretase inhibitor with PTE treatment may represent a novel approach for treating lung adenocarcinoma by inhibiting the survival pathways of cancer cells.

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Related in: MedlinePlus

The effects of PTE on the MMP of lung adenocarcinoma cells treated for 24 h.The MMP was estimated by flow cytometry after staining the cells with the fluorescent dye JC-1. Representative flow cytometry results are shown. The subpopulations and their fractions are indicated: normal MMP cells (upper right) and low MMP cells (low right). The MMP level was expressed as the proportion of cells with a low MMP. The results are expressed as the mean ± SEM, n = 6. **P<0.01 compared with the control group, ##P<0.01 compared with the PTE 1.5 µM group, $$P<0.01 compared with the PTE 3 µM group. PTE, pterostilbene; MMP, mitochondrial membrane potential.
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pone-0062652-g002: The effects of PTE on the MMP of lung adenocarcinoma cells treated for 24 h.The MMP was estimated by flow cytometry after staining the cells with the fluorescent dye JC-1. Representative flow cytometry results are shown. The subpopulations and their fractions are indicated: normal MMP cells (upper right) and low MMP cells (low right). The MMP level was expressed as the proportion of cells with a low MMP. The results are expressed as the mean ± SEM, n = 6. **P<0.01 compared with the control group, ##P<0.01 compared with the PTE 1.5 µM group, $$P<0.01 compared with the PTE 3 µM group. PTE, pterostilbene; MMP, mitochondrial membrane potential.

Mentions: After treatment with PTE (1.5, 3 or 6 µM) for 24 h, the proportion of cells with a low MMP increased significantly in a dose-dependent manner (P<0.01, compared with the control group, Figure 2). These results indicate that PTE can reduce the MMP of A549 cells.


Pterostilbene exerts antitumor activity via the Notch1 signaling pathway in human lung adenocarcinoma cells.

Yang Y, Yan X, Duan W, Yan J, Yi W, Liang Z, Wang N, Li Y, Chen W, Yu S, Jin Z, Yi D - PLoS ONE (2013)

The effects of PTE on the MMP of lung adenocarcinoma cells treated for 24 h.The MMP was estimated by flow cytometry after staining the cells with the fluorescent dye JC-1. Representative flow cytometry results are shown. The subpopulations and their fractions are indicated: normal MMP cells (upper right) and low MMP cells (low right). The MMP level was expressed as the proportion of cells with a low MMP. The results are expressed as the mean ± SEM, n = 6. **P<0.01 compared with the control group, ##P<0.01 compared with the PTE 1.5 µM group, $$P<0.01 compared with the PTE 3 µM group. PTE, pterostilbene; MMP, mitochondrial membrane potential.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3643961&req=5

pone-0062652-g002: The effects of PTE on the MMP of lung adenocarcinoma cells treated for 24 h.The MMP was estimated by flow cytometry after staining the cells with the fluorescent dye JC-1. Representative flow cytometry results are shown. The subpopulations and their fractions are indicated: normal MMP cells (upper right) and low MMP cells (low right). The MMP level was expressed as the proportion of cells with a low MMP. The results are expressed as the mean ± SEM, n = 6. **P<0.01 compared with the control group, ##P<0.01 compared with the PTE 1.5 µM group, $$P<0.01 compared with the PTE 3 µM group. PTE, pterostilbene; MMP, mitochondrial membrane potential.
Mentions: After treatment with PTE (1.5, 3 or 6 µM) for 24 h, the proportion of cells with a low MMP increased significantly in a dose-dependent manner (P<0.01, compared with the control group, Figure 2). These results indicate that PTE can reduce the MMP of A549 cells.

Bottom Line: PTE treatment resulted in a dose- and time-dependent decrease in the viability of A549 cells.DAPT (a gamma secretase inhibitor) and Notch1 siRNA prevented the induction of NICD and Hes1 activation by PTE treatment and sensitized the cells to PTE treatment.The down-regulation of Notch signaling also prevented the activation of pro-survival pathways (most notably the PI3K/Akt pathway) after PTE treatment.

View Article: PubMed Central - PubMed

Affiliation: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an City, China.

ABSTRACT
Although pterostilbene (PTE) has been shown to have potent antitumor activities against various cancer types, the molecular mechanisms of these activities remain unclear. In this study, we investigated the antitumor activity of PTE against human lung adenocarcinoma in vitro and in vivo and explored the role of the Notch1 signaling pathway in this process. PTE treatment resulted in a dose- and time-dependent decrease in the viability of A549 cells. Additionally, PTE exhibited strong antitumor activity, as evidenced not only by a reduced mitochondrial membrane potential (MMP) and a decreased intracellular glutathione content but also by increases in the apoptotic index and the level of reactive oxygen species (ROS). Furthermore, PTE treatment induced the activation of the Notch1 Intracellular Domain (NICD) protein and activated Hes1. DAPT (a gamma secretase inhibitor) and Notch1 siRNA prevented the induction of NICD and Hes1 activation by PTE treatment and sensitized the cells to PTE treatment. The down-regulation of Notch signaling also prevented the activation of pro-survival pathways (most notably the PI3K/Akt pathway) after PTE treatment. In summary, lung adenocarcinoma cells may enhance Notch1 activation as a protective mechanism in response to PTE treatment. Combining a gamma secretase inhibitor with PTE treatment may represent a novel approach for treating lung adenocarcinoma by inhibiting the survival pathways of cancer cells.

Show MeSH
Related in: MedlinePlus