2-Methoxy-5((3,4,5-trimethosyphenyl)seleninyl) phenol inhibits MDM2 and induces apoptosis in breast cancer cells through a p53-independent pathway
作者： Zengqiang Li , Daiying Zuo , Weige Zhang , Yingliang Wu , Jingwen Xu
DOI: 10.1016/J.CANLET.2016.09.011
关键词: Breast cancer 、 Mdm2 、 Combretastatin A-4 、 Cancer research 、 Transcription (biology) 、 Apoptosis 、 Phenol 、 Mutant 、 Combretastatin 、 Pharmacology 、 Biology
摘要: 2-Methoxy-5((3,4,5-trimethosyphenyl)seleninyl) phenol (SQ) is a novel synthesized combretastatin A-4 (CA-4) analog that can be classified as microtubule inhibitor. Our previous study demonstrated SQ induced G2/M phase arrest and promoted apoptosis progression in breast cancer cells. In the present study, we found dissociated MDM2-p53 complex directly MDM2 degradation through ubiquitin-dependent proteasome pathway MCF-7 MDA-MB-231 cells. Further, p53 was activated by regulation of its transcription, translation, post-translation modification. More specifically, caspase-dependent but p53-independent apoptosis, this associated with inhibition MDM2. We also showed exhibited superior in vivo efficacy low toxicity than CA-4. The immunofluorescence histochemistry indicated inhibited expression in vivo. summary, report for first time shows excellent anti-breast activity in vitro induces which inhibition. Therefore, compound has potential therapeutic treatment both wild-type mutant cancer.
sci-hub.se 参考文章(42)
Jiang-Jiang Qin, Wei Wang, Sukesh Voruganti, Hui Wang, Wei-Dong Zhang, Ruiwen Zhang, Identification of a new class of natural product MDM2 inhibitor: In vitro and in vivo anti-breast cancer activities and target validation Oncotarget. ,vol. 6, pp. 2623- 2640 ,(2015) , 10.18632/ONCOTARGET.3098
Dan Michael, Moshe Oren, The p53 and Mdm2 families in cancer. Current Opinion in Genetics & Development. ,vol. 12, pp. 53- 59 ,(2002) , 10.1016/S0959-437X(01)00264-7
Vivien E. Prise, George R. Pettit, Graham G. Dark, Sally A. Hill, Dai J. Chaplin, Gillian M. Tozer, Combretastatin A-4, an agent that displays potent and selective toxicity toward tumor vasculature Cancer Research. ,vol. 57, pp. 1829- 1834 ,(1997)
Kazushi Inoue, Elizabeth A. Fry, Donna P. Frazier, Transcription factors that interact with p53 and Mdm2. International Journal of Cancer. ,vol. 138, pp. 1577- 1585 ,(2016) , 10.1002/IJC.29663
Gina Marcela Méndez-Callejas, Stefano Leone, Caterina Tanzarella, Antonio Antoccia, Combretastatin A-4 induces p53 mitochondrial-relocalisation independent-apoptosis in non-small lung cancer cells. Cell Biology International. ,vol. 38, pp. 296- 308 ,(2014) , 10.1002/CBIN.10199
Zhuo Zhang, Ruiwen Zhang, None, p53-independent activities of MDM2 and their relevance to cancer therapy. Current Cancer Drug Targets. ,vol. 5, pp. 9- 20 ,(2005) , 10.2174/1568009053332618
Dmitry A Turbin, Maggie C U Cheang, Chris D Bajdik, Karen A Gelmon, Erika Yorida, Alessandro De Luca, Torsten O Nielsen, David G Huntsman, C Blake Gilks, MDM2 protein expression is a negative prognostic marker in breast carcinoma Modern Pathology. ,vol. 19, pp. 69- 74 ,(2006) , 10.1038/MODPATHOL.3800484
William R. Waud, Karen S. Gilbert, Steadman D. Harrison, Daniel P. Griswold, Cross-resistance of drug-resistant murine P388 leukemias to toxol in vivo Cancer Chemotherapy and Pharmacology. ,vol. 31, pp. 255- 257 ,(1992) , 10.1007/BF00685557
G. R. Pettit, S. B. Singh, E. Hamel, C. M. Lin, D. S. Alberts, D. Garcia-Kendal, Isolation and structure of the strong cell growth and tubulin inhibitor combretastatin A-4 Cellular and Molecular Life Sciences. ,vol. 45, pp. 209- 211 ,(1989) , 10.1007/BF01954881
G Ambrosini, E B Sambol, D Carvajal, L T Vassilev, S Singer, G K Schwartz, Mouse double minute antagonist Nutlin-3a enhances chemotherapy-induced apoptosis in cancer cells with mutant p53 by activating E2F1. Oncogene. ,vol. 26, pp. 3473- 3481 ,(2007) , 10.1038/SJ.ONC.1210136