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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 combined with DAPT on the Notch1 signaling and pro-survival factors in lung adenocarcinoma cells treated for 24 h.Representative Western blot results are shown. 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 6 µM group, $$P<0.01 compared with the PTE 6 µM+DAPT 10 µM group. PTE, pterostilbene.
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pone-0062652-g006: The effects of PTE combined with DAPT on the Notch1 signaling and pro-survival factors in lung adenocarcinoma cells treated for 24 h.Representative Western blot results are shown. The results are expressed as the mean ± SEM, n = 6. **P<0.01 compared with the control group, ##P<0.01 compared with the PTE 6 µM group, $$P<0.01 compared with the PTE 6 µM+DAPT 10 µM group. PTE, pterostilbene.

Mentions: A549 cells were treated with PTE (6 µM) combined with DAPT for 24 h, and the cell viability was then determined using an MTT assay. Treatment with PTE or DAPT alone decreased the cell viability (P<0.01, compared with the control group, Figure 5A). The combination of DAPT and PTE further decreased the cell viability (P<0.01, compared with the PTE 6 µM group or the DAPT 10 µM group, Figure 5A). In addition, the co-treatment of A549 cells with DAPT and PTE significantly increased the percentage of apoptotic cells compared with either treatment alone (P<0.01, Figure 5B). As expected, treatment with PTE and DAPT further inhibited NICD and Hes1 expression (Figure 6).


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 combined with DAPT on the Notch1 signaling and pro-survival factors in lung adenocarcinoma cells treated for 24 h.Representative Western blot results are shown. 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 6 µM group, $$P<0.01 compared with the PTE 6 µM+DAPT 10 µM group. PTE, pterostilbene.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0062652-g006: The effects of PTE combined with DAPT on the Notch1 signaling and pro-survival factors in lung adenocarcinoma cells treated for 24 h.Representative Western blot results are shown. 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 6 µM group, $$P<0.01 compared with the PTE 6 µM+DAPT 10 µM group. PTE, pterostilbene.
Mentions: A549 cells were treated with PTE (6 µM) combined with DAPT for 24 h, and the cell viability was then determined using an MTT assay. Treatment with PTE or DAPT alone decreased the cell viability (P<0.01, compared with the control group, Figure 5A). The combination of DAPT and PTE further decreased the cell viability (P<0.01, compared with the PTE 6 µM group or the DAPT 10 µM group, Figure 5A). In addition, the co-treatment of A549 cells with DAPT and PTE significantly increased the percentage of apoptotic cells compared with either treatment alone (P<0.01, Figure 5B). As expected, treatment with PTE and DAPT further inhibited NICD and Hes1 expression (Figure 6).

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