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BioMed Research International Volume 2017 ,2017-07-12
Pterostilbene Induces Cell Apoptosis and Cell Cycle Arrest in T-Cell Leukemia/Lymphoma by Suppressing the ERK1/2 Pathway
Research Article
Gaomei Chang 1 , 2 Wenqin Xiao 2 Zhijian Xu 3 , 4 Dandan Yu 2 Bo Li 3 Yong Zhang 3 Xi Sun 2 Yongsheng Xie 2 Shuaikang Chang 2 Lu Gao 2 Gege Chen 2 Liangning Hu 2 Bingqian Xie 2 Bojie Dai 5 Weiliang Zhu 3 Jumei Shi 1 , 2
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DOI:10.1155/2017/9872073
Received 2017-02-12, accepted for publication 2017-05-29, Published 2017-05-29
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摘要

Pterostilbene is a natural 3,5-dimethoxy analog of trans-resveratrol that has been reported to have antitumor, antioxidant, and anti-inflammatory effects. T-cell leukemia/lymphoma is one of the more aggressive yet uncommon non-Hodgkin lymphomas. Although there has been increasing research into T-cell leukemia/lymphoma, the molecular mechanisms of the antitumor effects of pterostilbene against this malignancy are still largely unknown. The aim of this study is to confirm the effects of pterostilbene in T-cell leukemia/lymphoma. Jurkat and Hut-78 cells treated with pterostilbene were evaluated for cell proliferation using Cell Counting Kit-8, and apoptosis, cell cycle progression, reactive oxygen species generation, and mitochondrial membrane potential were analyzed using flow cytometry. The level of protein expression was detected by western blot. The results demonstrated that pterostilbene significantly inhibited the growth of T-cell leukemia/lymphoma cell lines in vitro and induced apoptosis in a dose- and time-dependent manner. Moreover, pterostilbene treatment markedly induced S-phase cell cycle arrest, which was accompanied by downregulation of cdc25A, cyclin A2, and CDK2. Pterostilbene also induced the generation of reactive oxygen species and the loss of mitochondrial membrane potential and inhibited ERK1/2 phosphorylation. Taken together, our study demonstrated the potential of pterostilbene to be an effective treatment for T-cell leukemia/lymphoma.

授权许可

Copyright © 2017 Gaomei Chang et al. 2017
This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

图表

Pterostilbene and SCH772984 inhibit the growth of T-cell leukemia/lymphoma cells. (a, b) Jurkat and Hut-78 cells (2 × 105 cells/mL) were plated onto 96-well plates and treated with different concentrations (0, 10, 15, 20, 25, 30, 35, and 40 μM) of pterostilbene for 24 or 48 h. Data were represented as mean ± SD, n=3. P∗<0.05, compared to the control group. P#<0.05, compared to the 24 h group. (c) Jurkat and Hut-78 cells were treated with SCH772984 (0, 1, 2, 5, 10, and 20 μM) for 48 h. Data were represented as mean ± SD, n=3. P∗<0.05, compared to the control group. (d) Peripheral blood mononuclear cells (PBMCs) were treated with 0, 10, 20, 40, and 80 μM of pterostilbene for 48 h. Data were represented as mean ± SD, n=3. P∧>0.05, compared to the control group. The CCK-8 was used to evaluate these cells’ proliferation, with absorbance measured at 450 nm.

Pterostilbene and SCH772984 inhibit the growth of T-cell leukemia/lymphoma cells. (a, b) Jurkat and Hut-78 cells (2 × 105 cells/mL) were plated onto 96-well plates and treated with different concentrations (0, 10, 15, 20, 25, 30, 35, and 40 μM) of pterostilbene for 24 or 48 h. Data were represented as mean ± SD, n=3. P∗<0.05, compared to the control group. P#<0.05, compared to the 24 h group. (c) Jurkat and Hut-78 cells were treated with SCH772984 (0, 1, 2, 5, 10, and 20 μM) for 48 h. Data were represented as mean ± SD, n=3. P∗<0.05, compared to the control group. (d) Peripheral blood mononuclear cells (PBMCs) were treated with 0, 10, 20, 40, and 80 μM of pterostilbene for 48 h. Data were represented as mean ± SD, n=3. P∧>0.05, compared to the control group. The CCK-8 was used to evaluate these cells’ proliferation, with absorbance measured at 450 nm.

Pterostilbene and SCH772984 inhibit the growth of T-cell leukemia/lymphoma cells. (a, b) Jurkat and Hut-78 cells (2 × 105 cells/mL) were plated onto 96-well plates and treated with different concentrations (0, 10, 15, 20, 25, 30, 35, and 40 μM) of pterostilbene for 24 or 48 h. Data were represented as mean ± SD, n=3. P∗<0.05, compared to the control group. P#<0.05, compared to the 24 h group. (c) Jurkat and Hut-78 cells were treated with SCH772984 (0, 1, 2, 5, 10, and 20 μM) for 48 h. Data were represented as mean ± SD, n=3. P∗<0.05, compared to the control group. (d) Peripheral blood mononuclear cells (PBMCs) were treated with 0, 10, 20, 40, and 80 μM of pterostilbene for 48 h. Data were represented as mean ± SD, n=3. P∧>0.05, compared to the control group. The CCK-8 was used to evaluate these cells’ proliferation, with absorbance measured at 450 nm.

Pterostilbene and SCH772984 inhibit the growth of T-cell leukemia/lymphoma cells. (a, b) Jurkat and Hut-78 cells (2 × 105 cells/mL) were plated onto 96-well plates and treated with different concentrations (0, 10, 15, 20, 25, 30, 35, and 40 μM) of pterostilbene for 24 or 48 h. Data were represented as mean ± SD, n=3. P∗<0.05, compared to the control group. P#<0.05, compared to the 24 h group. (c) Jurkat and Hut-78 cells were treated with SCH772984 (0, 1, 2, 5, 10, and 20 μM) for 48 h. Data were represented as mean ± SD, n=3. P∗<0.05, compared to the control group. (d) Peripheral blood mononuclear cells (PBMCs) were treated with 0, 10, 20, 40, and 80 μM of pterostilbene for 48 h. Data were represented as mean ± SD, n=3. P∧>0.05, compared to the control group. The CCK-8 was used to evaluate these cells’ proliferation, with absorbance measured at 450 nm.

Pterostilbene and SCH772984 induce cell cycle arrest in T-cell leukemia/lymphoma cells. (a, c) Jurkat and Hut-78 cells were arrested in the S-phase treated with different concentrations of pterostilbene (0, 5, 10, and 20 μM) and SCH772984 10 μM for 24 h. (b, d) The percentage of G0/G1, G2M, and S-phase was indicated following various concentrations of pterostilbene and SCH772984 treatments. Data were represented as mean ± SD, n=3. P∗<0.05, compared to the control group. (e) The protein levels for 24 h of cdc25A, CDK2, and cyclin A2 were assessed by western blot. Data were represented as mean ± SD, n=3. P∗<0.05, compared to the control group.

Pterostilbene and SCH772984 induce caspase-dependent apoptosis in T-cell leukemia/lymphoma cells. (a) Jurkat cells (3 × 105 cells/mL) were treated with pterostilbene (0, 20, 40, and 80 μM) and incubated for 24 h or 48 h. Data were shown as mean ± SD, n=3. P∗<0.05, compared to the control group. P#<0.05, compared to the 24 h group. (b) Hut-78 cells (3 × 105 cells/mL) were treated with pterostilbene (0, 20, 40, and 80 μM) and incubated for 24 h or 48 h. Pterostilbene induced apoptosis of Jurkat and Hut-78 cells in a dose- and time-dependent manner. (c) Jurkat and Hut-78 cells were treated with SCH772984 10 μM for 48 h. Data were shown as mean ± SD, n=3. P∗<0.05, compared to the control group. (d) PBMCs and CD34+ cells from peripheral stem cells were treated with pterostilbene (0, 20, 40, and 80 μM), and pterostilbene was of toxicity to normal cells. Data were shown as mean ± SD, n=3. P∧>0.05, compared to the control group. (e) Protein levels treated with pterostilbene (0, 20, and 40 μM) of cleaved caspase-3, cleaved caspase-8, caspase-9, and PARP for 48 h were detected by western blot.

Pterostilbene and SCH772984 induce caspase-dependent apoptosis in T-cell leukemia/lymphoma cells. (a) Jurkat cells (3 × 105 cells/mL) were treated with pterostilbene (0, 20, 40, and 80 μM) and incubated for 24 h or 48 h. Data were shown as mean ± SD, n=3. P∗<0.05, compared to the control group. P#<0.05, compared to the 24 h group. (b) Hut-78 cells (3 × 105 cells/mL) were treated with pterostilbene (0, 20, 40, and 80 μM) and incubated for 24 h or 48 h. Pterostilbene induced apoptosis of Jurkat and Hut-78 cells in a dose- and time-dependent manner. (c) Jurkat and Hut-78 cells were treated with SCH772984 10 μM for 48 h. Data were shown as mean ± SD, n=3. P∗<0.05, compared to the control group. (d) PBMCs and CD34+ cells from peripheral stem cells were treated with pterostilbene (0, 20, 40, and 80 μM), and pterostilbene was of toxicity to normal cells. Data were shown as mean ± SD, n=3. P∧>0.05, compared to the control group. (e) Protein levels treated with pterostilbene (0, 20, and 40 μM) of cleaved caspase-3, cleaved caspase-8, caspase-9, and PARP for 48 h were detected by western blot.

Pterostilbene and SCH772984 induce caspase-dependent apoptosis in T-cell leukemia/lymphoma cells. (a) Jurkat cells (3 × 105 cells/mL) were treated with pterostilbene (0, 20, 40, and 80 μM) and incubated for 24 h or 48 h. Data were shown as mean ± SD, n=3. P∗<0.05, compared to the control group. P#<0.05, compared to the 24 h group. (b) Hut-78 cells (3 × 105 cells/mL) were treated with pterostilbene (0, 20, 40, and 80 μM) and incubated for 24 h or 48 h. Pterostilbene induced apoptosis of Jurkat and Hut-78 cells in a dose- and time-dependent manner. (c) Jurkat and Hut-78 cells were treated with SCH772984 10 μM for 48 h. Data were shown as mean ± SD, n=3. P∗<0.05, compared to the control group. (d) PBMCs and CD34+ cells from peripheral stem cells were treated with pterostilbene (0, 20, 40, and 80 μM), and pterostilbene was of toxicity to normal cells. Data were shown as mean ± SD, n=3. P∧>0.05, compared to the control group. (e) Protein levels treated with pterostilbene (0, 20, and 40 μM) of cleaved caspase-3, cleaved caspase-8, caspase-9, and PARP for 48 h were detected by western blot.

Pterostilbene and SCH772984 induce caspase-dependent apoptosis in T-cell leukemia/lymphoma cells. (a) Jurkat cells (3 × 105 cells/mL) were treated with pterostilbene (0, 20, 40, and 80 μM) and incubated for 24 h or 48 h. Data were shown as mean ± SD, n=3. P∗<0.05, compared to the control group. P#<0.05, compared to the 24 h group. (b) Hut-78 cells (3 × 105 cells/mL) were treated with pterostilbene (0, 20, 40, and 80 μM) and incubated for 24 h or 48 h. Pterostilbene induced apoptosis of Jurkat and Hut-78 cells in a dose- and time-dependent manner. (c) Jurkat and Hut-78 cells were treated with SCH772984 10 μM for 48 h. Data were shown as mean ± SD, n=3. P∗<0.05, compared to the control group. (d) PBMCs and CD34+ cells from peripheral stem cells were treated with pterostilbene (0, 20, 40, and 80 μM), and pterostilbene was of toxicity to normal cells. Data were shown as mean ± SD, n=3. P∧>0.05, compared to the control group. (e) Protein levels treated with pterostilbene (0, 20, and 40 μM) of cleaved caspase-3, cleaved caspase-8, caspase-9, and PARP for 48 h were detected by western blot.

Pterostilbene and SCH772984 induce caspase-dependent apoptosis in T-cell leukemia/lymphoma cells. (a) Jurkat cells (3 × 105 cells/mL) were treated with pterostilbene (0, 20, 40, and 80 μM) and incubated for 24 h or 48 h. Data were shown as mean ± SD, n=3. P∗<0.05, compared to the control group. P#<0.05, compared to the 24 h group. (b) Hut-78 cells (3 × 105 cells/mL) were treated with pterostilbene (0, 20, 40, and 80 μM) and incubated for 24 h or 48 h. Pterostilbene induced apoptosis of Jurkat and Hut-78 cells in a dose- and time-dependent manner. (c) Jurkat and Hut-78 cells were treated with SCH772984 10 μM for 48 h. Data were shown as mean ± SD, n=3. P∗<0.05, compared to the control group. (d) PBMCs and CD34+ cells from peripheral stem cells were treated with pterostilbene (0, 20, 40, and 80 μM), and pterostilbene was of toxicity to normal cells. Data were shown as mean ± SD, n=3. P∧>0.05, compared to the control group. (e) Protein levels treated with pterostilbene (0, 20, and 40 μM) of cleaved caspase-3, cleaved caspase-8, caspase-9, and PARP for 48 h were detected by western blot.

Pterostilbene induces MMP decline and ROS generation in T-cell leukemia/lymphoma cells. (a) Pterostilbene treatment (0, 20, 40, and 80 μM) for 48 h induced mitochondrial depolarization in Jurkat and Hut-78 cells. Data were shown as mean ± SD, n=3. P∗<0.05, compared to the control group. (b) Jurkat and Hut-78 cells treated with pterostilbene (0, 10 μM) for 48 h by flow cytometry. In the negative group, Jurkat and Hut-78 cells were treated without pterostilbene and DCFH-DA. Data were shown as mean ± SD, n=3. P∗<0.05, compared to the control group.

Pterostilbene induces MMP decline and ROS generation in T-cell leukemia/lymphoma cells. (a) Pterostilbene treatment (0, 20, 40, and 80 μM) for 48 h induced mitochondrial depolarization in Jurkat and Hut-78 cells. Data were shown as mean ± SD, n=3. P∗<0.05, compared to the control group. (b) Jurkat and Hut-78 cells treated with pterostilbene (0, 10 μM) for 48 h by flow cytometry. In the negative group, Jurkat and Hut-78 cells were treated without pterostilbene and DCFH-DA. Data were shown as mean ± SD, n=3. P∗<0.05, compared to the control group.

ERK1/2 phosphorylation was decreased following pterostilbene treatment for 48 h. (a) The expression levels of phospho-ERK1/2 and ERK1/2 were detected by western blot. Data were shown as mean ± SD, n=3. P∗<0.05, compared to the control group. (b) Jurkat and Hut-78 cells were treated with SCH772984 (10 μM) and pterostilbene (20 μM) for 48 h, and the expression levels of phospho-ERK1/2 and ERK1/2 were detected by western blot. Data were shown as mean ± SD, n=3. P∗<0.05, compared to the control group.

ERK1/2 phosphorylation was decreased following pterostilbene treatment for 48 h. (a) The expression levels of phospho-ERK1/2 and ERK1/2 were detected by western blot. Data were shown as mean ± SD, n=3. P∗<0.05, compared to the control group. (b) Jurkat and Hut-78 cells were treated with SCH772984 (10 μM) and pterostilbene (20 μM) for 48 h, and the expression levels of phospho-ERK1/2 and ERK1/2 were detected by western blot. Data were shown as mean ± SD, n=3. P∗<0.05, compared to the control group.

通讯作者

1. Weiliang Zhu.CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China, cas.cn.wlzhu@mail.shcnc.ac.cn
2. Jumei Shi.Department of Hematology, Anhui Medical University, Hefei 230032, China, ahmu.edu.cn;Department of Hematology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai 200072, China, tongji.edu.cn.shijumei@tongji.edu.cn

推荐引用方式

Gaomei Chang,Wenqin Xiao,Zhijian Xu,Dandan Yu,Bo Li,Yong Zhang,Xi Sun,Yongsheng Xie,Shuaikang Chang,Lu Gao,Gege Chen,Liangning Hu,Bingqian Xie,Bojie Dai,Weiliang Zhu,Jumei Shi. Pterostilbene Induces Cell Apoptosis and Cell Cycle Arrest in T-Cell Leukemia/Lymphoma by Suppressing the ERK1/2 Pathway. BioMed Research International ,Vol.2017(2017)

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