Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation
Yu, Zu-Yin1; Xiao, He2; Wang, Li-Mei1; Shen, Xing1; Jing, Yu3; Wang, Lin1; Sun, Wen-Feng1; Zhang, Yan-Feng1; Cui, Yu1; Shan, Ya-Jun1; Zhou, Wen-Bing1; Xing, Shuang1; Xiong, Guo-Lin1; Liu, Xiao-Lan1; Dong, Bo1; Feng, Jian-Nan2; Wang, Li-Sheng4; Luo, Qing-Liang1; Zhao, Qin-Shi5; Cong, Yu-Wen1
2016-05-01
Source PublicationCANCER RESEARCH
Volume76Issue:9Pages:2698-2709
AbstractAll-trans retinoic acid (ATRA)-based cell differentiation therapy has been successful in treating acute promyelocytic leukemia, a unique subtype of acute myeloid leukemia (AML). However, other subtypes of AML display resistance to ATRA-based treatment. In this study, we screened natural, plant-derived vibsane-type diterpenoids for their ability to induce differentiation of myeloid leukemia cells, discovering that vibsanin A potently induced differentiation of AML cell lines and primary blasts. The differentiation-inducing activity of vibsanin A was mediated through direct interaction with and activation of protein kinase C (PKC). Consistent with these findings, pharmacological blockade of PKC activity suppressed vibsanin A-induced differentiation. Mechanistically, vibsanin A-mediated activation of PKC led to induction of the ERK pathway and decreased c-Myc expression. In mouse xenograft models of AML, vibsanin A administration prolonged host survival and inhibited PKC-mediated inflammatory responses correlated with promotion of skin tumors in mice. Collectively, our results offer a preclinical proof of concept for vibsanin A as a myeloid differentiation-inducing compound, with potential application as an antileukemic agent. (C) 2016 AACR.
DOI10.1158/0008-5472.CAN-15-1616
Indexed BySCI
Language英语
WOS Research AreaOncology
WOS SubjectOncology
WOS IDWOS:000375332300020
Citation statistics
Cited Times:10[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.kib.ac.cn/handle/151853/26234
Collection植物化学与西部植物资源持续利用国家重点实验室
Affiliation1.Beijing Inst Radiat Med, Beijing Key Lab Radiobiol, Dept Pathophysiol, 27 Taiping Rd, Beijing 100850, Peoples R China
2.Chinese Acad Med Sci, Inst Basic Med Sci, Dept Mol Immunol, Beijing 100730, Peoples R China
3.Chinese Peoples Liberat Army Gen Hosp, Dept Hematol, Beijing 100853, Peoples R China
4.Beijing Inst Radiat Med, Dept Expt Hematol, 27 Taiping Rd, Beijing 100850, Peoples R China
5.Chinese Acad Sci, Kunming Inst Bot, State Key Lab Phytochem & Plant Resources West Ch, 132 Lanhei Rd, Kunming 650201, Yunnan, Peoples R China
Recommended Citation
GB/T 7714
Yu, Zu-Yin,Xiao, He,Wang, Li-Mei,et al. Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation[J]. CANCER RESEARCH,2016,76(9):2698-2709.
APA Yu, Zu-Yin.,Xiao, He.,Wang, Li-Mei.,Shen, Xing.,Jing, Yu.,...&Cong, Yu-Wen.(2016).Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation.CANCER RESEARCH,76(9),2698-2709.
MLA Yu, Zu-Yin,et al."Natural Product Vibsanin A Induces Differentiation of Myeloid Leukemia Cells through PKC Activation".CANCER RESEARCH 76.9(2016):2698-2709.
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