title: Pterostilbene induces apoptosis and cell cycle arrest in diffuse large B-cell lymphoma cells.
abstract: 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.
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Kong
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Gege
authors.initials: G
authors.lastname: Chen
authors.affiliation: CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Guang
authors.initials: G
authors.lastname: Yang
authors.affiliation: CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Xiaosong
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Wenqin
authors.initials: W
authors.lastname: Xiao
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Bingqian
authors.initials: B
authors.lastname: Xie
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Liangning
authors.initials: L
authors.lastname: Hu
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Sun
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Gaomei
authors.initials: G
authors.lastname: Chang
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Gao
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Gao
authors.affiliation: College of life science and technology, Tongji University, Shanghai, 200092, China.
authors.forename: Bojie
authors.initials: B
authors.lastname: Dai
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Tao
authors.affiliation: CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai, 201203, China.
authors.forename: Weiliang
authors.initials: W
authors.lastname: Zhu
authors.affiliation: Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
authors.forename: Jumei
authors.initials: J
authors.lastname: Shi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020169:Caspases / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D017382:Reactive Oxygen Species / Q000378:metabolism; D013267:Stilbenes / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D017382:Reactive Oxygen Species; D013267:Stilbenes; C107773:pterostilbene; D020169:Caspases