PMID- 27869675 OWN - NLM STAT- MEDLINE DCOM- 20170428 LR - 20181113 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 17 IP - 11 DP - 2016 Nov 17 TI - Pterostilbene Inhibits Human Multiple Myeloma Cells via ERK1/2 and JNK Pathway In Vitro and In Vivo. LID - 1927 AB - Multiple myeloma (MM) is the second most common malignancy in the hematologic system, which is characterized by accumulation of plasma cells in bone marrow. Pterostilbene (PTE) is a natural dimethylated analog of resveratrol, which has anti-oxidant, anti-inflammatory and anti-tumor properties. In the present study, we examined the anti-tumor effect of PTE on MM cell lines both in vitro and in vivo using the cell counting kit (CCK)-8, apoptosis assays, cell cycle analysis, reactive oxygen species (ROS) generation, JC-1 mitochondrial membrane potential assay, Western blotting and tumor xenograft models. The results demonstrated that PTE induces apoptosis in the H929 cell line and causes cell cycle arrest at G0/G1 phase by enhancing ROS generation and reducing mitochondrial membrane potential. The anti-tumor effect of PTE may be caused by the activation of the extracellular regulated protein kinases (ERK) 1/2 and c-Jun N-terminal kinase (JNK) signaling pathways. Additionally, mice treated with PTE by intraperitoneal injection demonstrated reduced tumor volume. Taken together, the results of this study indicate that the anti-tumor effect of PTE on MM cells may provide a new therapeutic option for MM patients. FAU - Xie, Bingqian AU - Xie B AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. xiebingqian0131@163.com. FAU - Xu, Zhijian AU - Xu Z AD - CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. zjxu@simm.ac.cn. FAU - Hu, Liangning AU - Hu L AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. inggiel@163.com. FAU - Chen, Gege AU - Chen G AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. 18767221930@163.com. FAU - Wei, Rong AU - Wei R AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. wei_rong001@163.com. FAU - Yang, Guang AU - Yang G AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. naiveyangboy@163.com. FAU - Li, Bo AU - Li B AD - CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. boli@simm.ac.cn. FAU - Chang, Gaomei AU - Chang G AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. 13162975523@163.com. FAU - Sun, Xi AU - Sun X AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. 15026573070@163.com. FAU - Wu, Huiqun AU - Wu H AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. whq19691208@163.com. FAU - Zhang, Yong AU - Zhang Y AD - CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. zhangyong109@simm.ac.cn. FAU - Dai, Bojie AU - Dai B AD - College of Life Science and Technology, Tongji University, Shanghai 200092, China. bojiedai@gmail.com. FAU - Tao, Yi AU - Tao Y AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. taoyi018@139.com. FAU - Shi, Jumei AU - Shi J AD - Department of Hematology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, China. shijumei@tongji.edu.cn. FAU - Zhu, Weiliang AU - Zhu W AD - CAS Key Laboratory of Receptor Research, Drug Discovery and Design Center, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China. wlzhu@simm.ac.cn. LA - eng PT - Journal Article DEP - 20161117 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Antineoplastic Agents) RN - 0 (Reactive Oxygen Species) RN - 0 (Stilbenes) RN - 26R60S6A5I (pterostilbene) SB - IM MH - Animals MH - Antineoplastic Agents/*pharmacology/therapeutic use MH - Apoptosis/drug effects MH - Cell Line, Tumor MH - Cell Proliferation/drug effects MH - DNA Damage MH - Female MH - G1 Phase Cell Cycle Checkpoints MH - Humans MH - MAP Kinase Signaling System/*drug effects MH - Membrane Potential, Mitochondrial/drug effects MH - Mice, Inbred NOD MH - Mice, SCID MH - Multiple Myeloma/*drug therapy/metabolism MH - Reactive Oxygen Species/metabolism MH - Stilbenes/*pharmacology/therapeutic use MH - Tumor Burden MH - Xenograft Model Antitumor Assays PMC - PMC5133923 OTO - NOTNLM OT - ERK1/2 OT - JNK OT - apoptosis OT - cell cycle OT - multiple myeloma OT - pterostilbene COIS- The authors declare no conflict of interest. EDAT- 2016/11/22 06:00 MHDA- 2017/04/30 06:00 PMCR- 2016/11/01 CRDT- 2016/11/22 06:00 PHST- 2016/09/22 00:00 [received] PHST- 2016/11/06 00:00 [revised] PHST- 2016/11/10 00:00 [accepted] PHST- 2016/11/22 06:00 [entrez] PHST- 2016/11/22 06:00 [pubmed] PHST- 2017/04/30 06:00 [medline] PHST- 2016/11/01 00:00 [pmc-release] AID - ijms17111927 [pii] AID - ijms-17-01927 [pii] AID - 10.3390/ijms17111927 [doi] PST - epublish SO - Int J Mol Sci. 2016 Nov 17;17(11):1927. doi: 10.3390/ijms17111927.