Pterostilbene induces apoptosis and cell cycle arrest in diffuse large B-cell lymphoma cells

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作者
Yuanyuan Kong
Gege Chen
Zhijian Xu
Guang Yang
Bo Li
Xiaosong Wu
Wenqin Xiao
Bingqian Xie
Liangning Hu
Xi Sun
Gaomei Chang
Minjie Gao
Lu Gao
Bojie Dai
Yi Tao
Weiliang Zhu
Jumei Shi
机构
[1] Shanghai Tenth People’s Hospital,Department of Hematology
[2] Tongji University School of Medicine,undefined
[3] CAS Key Laboratory of Receptor Research,undefined
[4] Drug Discovery and Design Center,undefined
[5] Shanghai Institute of Materia Medica,undefined
[6] Chinese Academy of Sciences,undefined
[7] College of life science and technology,undefined
[8] Tongji University,undefined
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摘要
Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma (NHL). Pterostilbene, a natural dimethylated analog of resveratrol, has been shown to possess diverse pharmacological activities, including anti-inflammatory, antioxidant and anticancer properties. However, to the best of our knowledge, there has been no study of the effects of pterostilbene upon hematological malignancies. Herein, we report the antitumor activity and mechanism of pterostilbene against DLBCL cells both in vitro and in vivo. We found that pterostilbene treatment resulted in a dose-dependent inhibition of cell viability. In addition, pterostilbene exhibited a strong cytotoxic effect, as evidenced not only by reductions of mitochondrial membrane potential (MMP) but also by increases in cellular apoptotic index and reactive oxygen species (ROS) levels, leading to arrest in the S-phase of the cell cycle. Furthermore, pterostilbene treatment directly up-regulated p-p38MAPK and down-regulated p-ERK1/2. In vivo, intravenous administration of pterostilbene inhibited tumor development in xenograft mouse models. Overall, the results suggested that pterostilbene is a potential anti-cancer pharmaceutical against human DLBCL by a mechanism involving the suppression of ERK1/2 and activation of p38MAPK signaling pathways.
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