姜黄素类似物EF24的抗肿瘤机制与应用

doi:10.3760/cma.j.issn.1673-422X.2018.03.010

国际肿瘤学杂志 ›› 2018, Vol. 45 ›› Issue (3): 172-175.doi: 10.3760/cma.j.issn.1673-422X.2018.03.010

姜黄素类似物EF24的抗肿瘤机制与应用

凌晓斐，胥可，邵华，王翠娟

250062 济南大学山东省医学科学院医学与生命科学学院(凌晓斐、胥可)；山东省医学科学院山东省职业卫生与职业病防治研究院理化实验室（凌晓斐、胥可、邵华、王翠娟）

收稿日期:2017-12-22 出版日期:2018-03-08 发布日期:2018-05-16
通讯作者: 邵华，Email: chinashaohua5888@163.com；王翠娟，Email: iamcuijuan@163.com E-mail:邵华，Email: chinashaohua5888@163.com；王翠娟，Email: iamcuijuan@163.com

Anticancer mechanism and application of curcumin analog EF24

Ling Xiaofei, Xu Ke, Shao Hua, Wang Cuijuan

School of Medicine and Life Sciences, University of Ji′nanShandong Academy of Medical Sciences; Physics and Chemistry Laboratory, Shandong Academy of Occupational Health and Occupational Medicine, Shandong Academy of Medical Sciences, Ji′nan 250062, China

Received:2017-12-22 Online:2018-03-08 Published:2018-05-16
Contact: 邵华，Email: chinashaohua5888@163.com；王翠娟，Email: iamcuijuan@163.com E-mail:邵华，Email: chinashaohua5888@163.com；王翠娟，Email: iamcuijuan@163.com

摘要/Abstract

摘要： 姜黄素是从姜黄属植物姜黄根茎中提取的酚性色素，具有抗氧化、抗炎、抗肿瘤等多方面药理作用。研究表明，联苯二氟铜（EF24）是一种新型姜黄素类似物，EF24可以诱导肿瘤细胞凋亡、阻滞细胞周期、抑制细胞侵袭与转移，与其他药物联合使用时具有增敏效果，在不增加细胞毒性的情况下，在多种肿瘤细胞株中表现出比姜黄素更高的抗肿瘤活性与生物利用度，有望作为一种具有潜力的抗癌新药。

关键词: 抗肿瘤药, 姜黄素, 联苯二氟铜

Abstract: Curcumin is a polyphenol pigment product from the rhizome of curcumin longa. It is associated with numerous therapeutic benefits, including antioxidant, antiinflammatory and anticancer activities. Research shows that EF24 is a curcumin analog that can induce tumor cell apoptosis, arrest cell cycle, inhibit cell invasion and metastasis and has synergistic effect of combined antitumor agents. EF24 has improved anticancer activity and bioavailability against various cancer cell lines over curcumin without increased toxicity. EF24 would have great potential to be used as a useful therapeutic agent for the treatment of various types of cancer.

Key words: Antineoplastic agents, Curcumin, EF24

凌晓斐，胥可，邵华，王翠娟. 姜黄素类似物EF24的抗肿瘤机制与应用 [J]. 国际肿瘤学杂志, 2018, 45(3): 172-175.

Ling Xiaofei, Xu Ke, Shao Hua, Wang Cuijuan. Anticancer mechanism and application of curcumin analog EF24[J]. Journal of International Oncology, 2018, 45(3): 172-175.

参考文献

［1］ Wu JZ, Wu SB, Shi LY, et al. Design, synthesis, and evaluation of asymmetric EF24 analogues as potential anticancer agents for lung cancer［J］. Eur J Med Chem, 2017, 125: 1321-1331. DOI: 10.1016/j.ejmech.2016.10.027. ［2］韩金荣, 张林西. 姜黄素抗肿瘤作用机制［J］. 国际肿瘤学杂志, 2013, 40(11): 823-826. DOI: 10.3760/cma.j.issn.1673-422X.2013.11.007. ［3］ Bisht S, Schlesinger M, Rupp A, et al. A liposomal formulation of the synthetic curcumin analog EF24 (LipoEF24) inhibits pancreatic cancer progression: towards future combination therapies［J］. J Nanobiotechnology, 2016, 14(1): 57. DOI: 10.1186/s12951-016-0209-6. ［4］ He G, Feng C, Vinothkumar R, et al. Curcumin analog EF24 induces apoptosis via ROSdependent mitochondrial dysfunction in human colorectal cancer cells［J］. Cancer Chemother Pharmacol, 2016, 78(6): 1151-1161. DOI: 10.1007/s00280-016-3172-x. ［5］ Yang CH, Yue J, Sims M, et al. The curcumin analog EF24 targets NFκB and miRNA-21, and has potent anticancer activity in vitro and in vivo［J］. PLoS One, 2013, 8(8): e71130. DOI: 10.1371/journal.pone.0071130. ［6］ Kasinski AL, Du Y, Thomas SL, et al. Inhibition of IkappaB kinasenuclear factorkappaB signaling pathway by 3,5bis(2flurobenzylidene)piperidin4one (EF24), a novel monoketone analog of curcumin［J］. Mol Pharmacol, 2008, 74(3): 654661. DOI: 10.1124/mol.108.046201. ［7］ Yin DL, Liang YJ, Zheng TS, et al. EF24 inhibits tumor growth and metastasis via suppressing NFkappaB dependent pathways in human cholangiocarcinoma［J］. Sci Rep, 2016, 6: 32167. DOI: 10.1038/srep32167. ［8］ Raj L, Ide T, Gurkar AU, et al. Selective killing of cancer cells by a small molecule targeting the stress response to ROS［J］. Nature, 2011, 475(7355): 231-234. DOI: 10.1038/nature10167. ［9］ Peng Z, Xia Y, Chen W, et al. EF24 induces ROSmediated apoptosis via targeting thioredoxin reductase 1 in gastric cancer cells［J］. Oncotarget, 2016, 7(14): 18050-18064. ［10］ Thomas SL, Zhong D, Zhou W, et al. EF24, a novel curcumin analog, disrupts the microtubule cytoskeleton and inhibits HIF1［J］. Cell Cycle, 2008, 7(15): 2409-2417. DOI: 10.4161/cc.6410. ［11］ Fragkos M, Ganier O, Coulombe P, et al. DNA replication origin activation in space and time［J］. Nat Rev Mol Cell Biol, 2015, 16(6): 360-374. DOI: 10.1038/nrm4002. ［12］ Liu HT, Liang YJ, Wang LL, et al. In vivo and in vitro suppression of hepatocellular carcinoma by EF24, a curcumin analog［J］. PLoS One, 2012, 7(10): e48075. DOI: 10.1371/journal.pone.0048075. ［13］ Meek DW. Regulation of the p53 response and its relationship to cancer［J］. Biochem J, 2015, 469(3): 325-346. DOI: 10.1042/BJ20150517. ［14］ Subramaniam D, May R, Sureban SM, et al. Diphenyl difluoroketone: a curcumin derivative with potent in vivo anticancer activity［J］. Cancer Res, 2008, 68(6): 1962-1969. DOI: 10.1158/00085472.CAN-07-6011. ［15］ Dvorak HF. Tumors: wounds that do not healredux［J］. Cancer Immunol Res, 2015, 3(1): 1-11. DOI: 10.1158/23266066.CIR-14-0209. ［16］李纯苓, 王朝霞, 王恒孝. HIF1α、PDGF与VEGF、VEGFR在乳腺癌发病中的表达及意义［J］. 国际肿瘤学杂志, 2014, 41(11): 858-865. DOI: 10.3760/cma.j.issn.1673-422X.2014.11.018. ［17］ Liu W, Kovacevic Z, Peng Z, et al. The molecular effect of metastasis suppressors on Src signaling and tumorigenesis: new therapeutic targets［J］. Oncotarget, 2015, 6(34): 35522-35541. DOI: 10.18632/oncotarget.5849. ［18］ Zhao R, Tin L, Zhang Y, et al. EF24 suppresses invasion and migration of hepatocellular carcinoma cells in vitro via inhibiting the phosphorylation of Src［J］. Biomed Res Int, 2016, 2016: 8569684. DOI: 10.1155/2016/8569684. ［19］曹纯, 马晓洁, 谭榜宪. 缺氧诱导因子-1α与上皮间质转化［J］. 国际肿瘤学杂志, 2014, 41(6): 415-418. DOI: 10.3760/cma.j.issn.1673-422X.2014.06.005. ［20］ Zhang P, Bai H, Liu G, et al. MicroRNA33b, upregulated by EF24, a curcumin analog, suppresses the epithelialtomesenchymal transition (EMT) and migratory potential of melanoma cells by targeting HMGA2［J］. Toxicol Lett, 2015, 234(3): 151161. DOI: 10.1016/j.toxlet.2015.02.018. ［21］ Zhang D, Wang Y, Dong L, et al. Therapeutic role of EF24 targeting glucose transporter 1mediated metabolism and metastasis in ovarian cancer cells［J］. Cancer Sci, 2013, 104(12): 1690-1696. DOI: 10.1111/cas.12293. ［22］ Liang Y, Yin D, Hou L, et al. Diphenyl difluoroketone: a potent chemotherapy candidate for human hepatocellular carcinoma［J］. PLoS One, 2011, 6(8): e23908. DOI: 10.1371/journal.pone.0023908. ［23］ Chen W, Zou P, Zhao Z, et al. Synergistic antitumor activity of rapamycin and EF24 via increasing ROS for the treatment of gastric cancer［J］. Redox Biol, 2016, 10: 78-89. DOI: 10.1016/j.redox.2016.09.006. ［24］ Onen HI, Yilmaz A, Alp E, et al. EF24 and RAD001 potentiates the anticancer effect of platinumbased agents in human malignant pleural mesothelioma (MSTO211H) cells and protects nonmalignant mesothelial (MET5A) cells［J］. Hum Exp Toxicol, 2015, 34(2): 117-126. DOI: 10.1177/0960327114542965. ［25］ Liang Y, Zheng T, Song R, et al. Hypoxiamediated sorafenib resistance can be overcome by EF24 through Von HippelLindau tumor suppressordependent HIF-1α inhibition in hepatocellular carcinoma［J］. Hepatology, 2013, 57(5): 1847-1857. DOI: 10.1002/hep.26224. ［26］ Aravindan S, Natarajan M, Awasthi V, et al. Novel synthetic monoketone transmute radiationtriggered NFκBdependent TNFα crosssignaling feedback maintained NFκB and favors neuroblastoma regression［J］. PLoS One, 2013, 8(8): e72464. DOI: 10.1371/journal.pone.0072464.

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姜黄素类似物EF24的抗肿瘤机制与应用

Anticancer mechanism and application of curcumin analog EF24

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