4.6

CiteScore

2.2

Impact Factor
  • ISSN 1674-8301
  • CN 32-1810/R
Jiang-Jiang Qin, Sushanta Sarkar, Sukesh Voruganti, Rajesh Agarwal, Wei Wang, Ruiwen Zhang. Identification of lineariifolianoid A as a novel dual NFAT1 and MDM2 inhibitor for human cancer therapy[J]. The Journal of Biomedical Research, 2016, 30(4): 322-333. DOI: 10.7555/JBR.30.20160018
Citation: Jiang-Jiang Qin, Sushanta Sarkar, Sukesh Voruganti, Rajesh Agarwal, Wei Wang, Ruiwen Zhang. Identification of lineariifolianoid A as a novel dual NFAT1 and MDM2 inhibitor for human cancer therapy[J]. The Journal of Biomedical Research, 2016, 30(4): 322-333. DOI: 10.7555/JBR.30.20160018

Identification of lineariifolianoid A as a novel dual NFAT1 and MDM2 inhibitor for human cancer therapy

Funds: 

the National Institutes of Health (NIH) grant R01 CA186662 (to R.Z.) , CA102514 (to R.A.),and American Cancer Society (ACS) grant RSG-15-009-01-CDD (to W.W.)

More Information
  • Received Date: January 28, 2016
  • Revised Date: February 21, 2016
  • There is an increasing interest in development of novel anticancer agents that target oncogenes. We have recently discovered that nuclear factor of activated T cells 1 (NFAT1) is a novel regulator of the Mouse Double Minute 2 (MDM2) oncogene and the NFAT1-MDM2 pathway has been implicated in human cancer development and progression, justifying that targeting the NFAT1-MDM2 pathway could be a novel strategy for discovery and development of novel cancer therapeutics. The present study was designed to examine the anticancer activity and underlying mechanisms of action of lineariifolianoid A (LinA), a novel natural product inhibitor of the NFAT1-MDM2 pathway. The cytotoxicity of LinA was first tested in various human cancer cell lines in comparison with normal cell lines. The results showed that the breast cancer cells were highly sensitive to LinA treatment. We next demonstrated the effects of LinA on cell proliferation, colony formation, cell cycle progression, and apoptosis in breast cancer MCF7 and MDA-MB-231 cells, in dose-dependent and p53-independent manners. LinA also inhibited the migration and invasion of these cancer cells. Our mechanistic studies further indicated that its anticancer activities were attributed to its inhibitory effects on the NFAT1-MDM2 pathway and modulatory effects on the expression of key proteins involved in cell cycle progression, apoptosis, and DNA damage. In summary, LinA is a novel NFAT1-MDM2 inhibitor and may be developed as a preventive and therapeutic agent against human cancer.
  • Related Articles

    [1]Dongmei Zhu, Lingli Luo, Hanjie Zeng, Zheng Zhang, Min Huang, Suming Zhou. Knockdown of 11β-hydroxysteroid dehydrogenase type 1 alleviates LPS-induced myocardial dysfunction through the AMPK/SIRT1/PGC-1α pathway[J]. The Journal of Biomedical Research, 2023, 37(4): 290-301. DOI: 10.7555/JBR.36.20220212
    [2]Wang Lei, Zhang Kun, Ding Xin, Wang Yan, Bai Hui, Yang Qing, Ben Jingjing, Zhang Hanwen, Li Xiaoyu, Chen Qi, Zhu Xudong. Fucoidan antagonizes diet-induced obesity and inflammation in mice[J]. The Journal of Biomedical Research, 2021, 35(3): 197-205. DOI: 10.7555/JBR.34.20200153
    [3]Venakatesh Archana G., Mathew Johann J., Coleman Scott, Yang Longqiu, Liu Geoffrey L., Li Marilyn M., Liu Henry. Effects of milrinone on inflammatory response-related gene expressions in cultured rat cardiomyocytes[J]. The Journal of Biomedical Research, 2019, 33(4): 258-263. DOI: 10.7555/JBR.32.20170085
    [4]Alireza Shirpoor, Farzaneh Hosseini Gharalari, Yousef Rasmi, Elaheh Heshmati. Ginger extract attenuates ethanol-induced pulmonary histological changes and oxidative stress in rats[J]. The Journal of Biomedical Research, 2017, 31(6): 521-527. DOI: 10.7555/JBR.31.20160151
    [5]Qin Wei, Yeping Bian, Fuchao Yu, Qiang Zhang, Guanghao Zhang, Yang Li, Songsong Song, Xiaomei Ren, Jiayi Tong. Chronic intermittent hypoxia induces cardiac inflammation and dysfunction in a rat obstructive sleep apnea model[J]. The Journal of Biomedical Research, 2016, 30(6): 490-495. DOI: 10.7555/JBR.30.20160110
    [6]Iyaswamy Ashok, Rathinasamy Sheeladevi, Dapkupar Wankhar. Acute effect of aspartame-induced oxidative stress in Wistar albino rat brain[J]. The Journal of Biomedical Research, 2015, 29(5): 390-396. DOI: 10.7555/JBR.28.20120118
    [7]Guoliang Meng, Jing Wang, Yujiao Xiao, Wenli Bai, Liping Xie, Liyang Shan, Philip K Moore, Yong Ji. GYY4137 protects against myocardial ischemia and reperfusion injury by attenuating oxidative stress and apoptosis in rats[J]. The Journal of Biomedical Research, 2015, 29(3): 203-213. DOI: 10.7555/JBR.28.20140037
    [8]Venkatashivam Shiva Kumar, Anuchandra Ramchandra Rajmane, Mohammad Adil, Amit Dattatraya Kandhare, Pinaki Ghosh, Subhash Laxman Bodhankar. Naringin ameliorates acetic acid induced colitis through modulation of endogenous oxido-nitrosative balance and DNA damage in rats[J]. The Journal of Biomedical Research, 2014, 28(2): 132-145. DOI: 10.7555/JBR.27.20120082
    [9]Ze Guo, Bingrong Zhou, Wei Li, Xuejun Sun, Dan Luo. Hydrogen-rich saline protects against ultraviolet B radiation injury in rats[J]. The Journal of Biomedical Research, 2012, 26(5): 365-371. DOI: 10.7555/JBR.26.20110037
    [10]Bo Cui, Stewart P. Johnson, Nancy Bullock, Francis Ali-Osman, Darell D. Bigner, Henry S. Friedman. Decoupling of DNA damage response signaling from DNA damages underlies temozolomide resistance in glioblastoma cells[J]. The Journal of Biomedical Research, 2010, 24(6): 424-435. DOI: 10.1016/S1674-8301(10)60057-7

Catalog

    Article Metrics

    Article views PDF downloads Cited by()
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return