A new oridonin analog suppresses triple-negative breast cancer cells and tumor growth via the induction of death receptor 5 | |
Wu J1,2,3; Ding Y4; Chen HY4; Zhou J[*]4; Chen CS[*]1; Chen CH1; Zhou ZM1; Ding CY4 | |
刊名 | CANCER LETTERS |
2016 | |
卷号 | 380期号:2页码:393-402 |
关键词 | Oridonin analog Apoptosis Death receptor 5 (DR5) Triple-negative breast cancer Therapy |
通讯作者 | jizhou@utmb.edu ; chenc@mail.kiz.ac.cn |
合作状况 | 其它 |
英文摘要 | Triple-negative breast cancer (TNBC) remains the leading cause of death among women with breast cancer worldwide. Oridonin is a natural anti-cancer compound that is isolated from the traditional Chinese herb Rabdosia rubescens. However, the antitumor efficacies of oridonin in the treatments of TNBC and other cancers are far from ideal. In this study, we investigated a series of newly designed oridonin analogs in terms of their actions against HCC1806 and HCC1937 TNBC cell lines and identified CYD-6-28, which significantly inhibits cancer cell proliferation and induces G2/M-phase cell cycle arrest and apoptosis. CYD-6-28 induces the expression of p21 and the cleavage of caspase-3,-7,-8 and PARP and inhibits the expression levels of Cyclin D1, FLIPS and XIAP. CYD-6-28 also inhibits the activations of STAT3 and AKT and induces the activation of ERK. We demonstrated that CYD-6-28 induces apoptosis at least partially by inducing the expression of death receptor 5 (DR5). Finally, CYD-6-28 significantly suppresses HCC1806 xenograft tumor growth in nude mice at 5 mg/kg without affecting body weight. Taken together, these results indicate that CYD-6-28 has the potential to be developed as a therapeutic agent to treat TNBC. |
收录类别 | SCI |
资助信息 | This work was supported by the National Natural Science Foun- dation of China (81120108019 and 81325016 to Chen, C), Chinese Postdoctoral Science Foundation Grant 2015M582581 to Chen, C.H, grants P30 DA028821 and R01 DA038446 from the National Insti- tutes of Health, and a Cancer Prevention Research Institute of Texas (CPRIT) award (to Zhou, J). |
语种 | 英语 |
内容类型 | 期刊论文 |
源URL | [http://159.226.149.26:8080/handle/152453/10594] |
专题 | 昆明动物研究所_肿瘤生物学 昆明动物研究所_动物模型与人类重大疾病机理重点实验室 |
作者单位 | 1.Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences and Yunnan Province, Chinese Academy of Sciences, Kunming Institute of Zoology, Kunming, Yunnan 650223, China 2.Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China 3.Department of Biochemistry and Molecular Biology, Kunming Medical University, Kunming, Yunnan 650500, China 4.Chemical Biology Program, Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston, TX 77555, United States |
推荐引用方式 GB/T 7714 | Wu J,Ding Y,Chen HY,et al. A new oridonin analog suppresses triple-negative breast cancer cells and tumor growth via the induction of death receptor 5[J]. CANCER LETTERS,2016,380(2):393-402. |
APA | Wu J.,Ding Y.,Chen HY.,Zhou J[*].,Chen CS[*].,...&Ding CY.(2016).A new oridonin analog suppresses triple-negative breast cancer cells and tumor growth via the induction of death receptor 5.CANCER LETTERS,380(2),393-402. |
MLA | Wu J,et al."A new oridonin analog suppresses triple-negative breast cancer cells and tumor growth via the induction of death receptor 5".CANCER LETTERS 380.2(2016):393-402. |
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