The Efficacy and Safety of Caffeic Acid for Esophageal Cancer

Summary

Caffeic acid can target inhibit GASC1 (gene amplified in squamous cell carcinoma 1, also known as KDM4C and JMJD2C) expression and GASC1 is confirmed to be a new oncogene in several cancers including esophageal cancer. This study aims to investigate the efficiency and safety of coffeic acid in chinese advanced esophageal squamous cell cancer (ESCC).

Timeline

Start

2017-01

Primary completion

2020-12

Completion

2021-12

Publications

• Background Li S, Zhang W, Yang Y, Ma T, Guo J, Wang S, Yu W, Kong L. Discovery of oral-available resveratrol-caffeic acid based hybrids inhibiting acetylated and phosphorylated STAT3 protein. Eur J Med Chem. 2016 Nov 29;124:1006-1018. doi: 10.1016/j.ejmech.2016.10.028. Epub 2016 Oct 15.
• Results Pedersen MT, Kooistra SM, Radzisheuskaya A, Laugesen A, Johansen JV, Hayward DG, Nilsson J, Agger K, Helin K. Continual removal of H3K9 promoter methylation by Jmjd2 demethylases is vital for ESC self-renewal and early development. EMBO J. 2016 Jul 15;35(14):1550-64. doi: 10.15252/embj.201593317. Epub 2016 Jun 6.
• Results Movassaghian S, Xie Y, Hildebrandt C, Rosati R, Li Y, Kim NH, Conti DS, da Rocha SR, Yang ZQ, Merkel OM. Post-Transcriptional Regulation of the GASC1 Oncogene with Active Tumor-Targeted siRNA-Nanoparticles. Mol Pharm. 2016 Aug 1;13(8):2605-21. doi: 10.1021/acs.molpharmaceut.5b00948. Epub 2016 Jun 27.
• Results Sudo G, Kagawa T, Kokubu Y, Inazawa J, Taga T. Increase in GFAP-positive astrocytes in histone demethylase GASC1/KDM4C/JMJD2C hypomorphic mutant mice. Genes Cells. 2016 Mar;21(3):218-25. doi: 10.1111/gtc.12331. Epub 2016 Jan 25.
• Results Ye Q, Holowatyj A, Wu J, Liu H, Zhang L, Suzuki T, Yang ZQ. Genetic alterations of KDM4 subfamily and therapeutic effect of novel demethylase inhibitor in breast cancer. Am J Cancer Res. 2015 Mar 15;5(4):1519-30. eCollection 2015.
• Results Ozaki Y, Fujiwara K, Ikeda M, Ozaki T, Terui T, Soma M, Inazawa J, Nagase H. The oncogenic role of GASC1 in chemically induced mouse skin cancer. Mamm Genome. 2015 Dec;26(11-12):591-7. doi: 10.1007/s00335-015-9592-9. Epub 2015 Aug 7.
• Results Sun LL, Wu JY, Wu ZY, Shen JH, Xu XE, Chen B, Wang SH, Li EM, Xu LY. A three-gene signature and clinical outcome in esophageal squamous cell carcinoma. Int J Cancer. 2015 Mar 15;136(6):E569-77. doi: 10.1002/ijc.29211. Epub 2014 Sep 24.
• Results Uimonen K, Merikallio H, Paakko P, Harju T, Mannermaa A, Palvimo J, Kosma VM, Soini Y. GASC1 expression in lung carcinoma is associated with smoking and prognosis of squamous cell carcinoma. Histol Histopathol. 2014 Jun;29(6):797-804. doi: 10.14670/HH-29.797. Epub 2013 Dec 27.
• Results Sun LL, Holowatyj A, Xu XE, Wu JY, Wu ZY, Shen JH, Wang SH, Li EM, Yang ZQ, Xu LY. Histone demethylase GASC1, a potential prognostic and predictive marker in esophageal squamous cell carcinoma. Am J Cancer Res. 2013 Nov 1;3(5):509-17. eCollection 2013.
• Results Berdel B, Nieminen K, Soini Y, Tengstrom M, Malinen M, Kosma VM, Palvimo JJ, Mannermaa A. Histone demethylase GASC1--a potential prognostic and predictive marker in invasive breast cancer. BMC Cancer. 2012 Nov 14;12:516. doi: 10.1186/1471-2407-12-516.
• Results Liu G, Bollig-Fischer A, Kreike B, van de Vijver MJ, Abrams J, Ethier SP, Yang ZQ. Genomic amplification and oncogenic properties of the GASC1 histone demethylase gene in breast cancer. Oncogene. 2009 Dec 17;28(50):4491-500. doi: 10.1038/onc.2009.297. Epub 2009 Sep 28.
• Results Yuan X, Kong J, Ma Z, Li N, Jia R, Liu Y, Zhou F, Zhan Q, Liu G, Gao S. KDM4C, a H3K9me3 Histone Demethylase, is Involved in the Maintenance of Human ESCC-Initiating Cells by Epigenetically Enhancing SOX2 Expression. Neoplasia. 2016 Oct;18(10):594-609. doi: 10.1016/j.neo.2016.08.005. Epub 2016 Sep 19.
• Results Tyszka-Czochara M, Konieczny P, Majka M. Caffeic Acid Expands Anti-Tumor Effect of Metformin in Human Metastatic Cervical Carcinoma HTB-34 Cells: Implications of AMPK Activation and Impairment of Fatty Acids De Novo Biosynthesis. Int J Mol Sci. 2017 Feb 21;18(2):462. doi: 10.3390/ijms18020462.
• Results Bonuccelli G, De Francesco EM, de Boer R, Tanowitz HB, Lisanti MP. NADH autofluorescence, a new metabolic biomarker for cancer stem cells: Identification of Vitamin C and CAPE as natural products targeting "stemness". Oncotarget. 2017 Mar 28;8(13):20667-20678. doi: 10.18632/oncotarget.15400.
• Results Chung LC, Chiang KC, Feng TH, Chang KS, Chuang ST, Chen YJ, Tsui KH, Lee JC, Juang HH. Caffeic acid phenethyl ester upregulates N-myc downstream regulated gene 1 via ERK pathway to inhibit human oral cancer cell growth in vitro and in vivo. Mol Nutr Food Res. 2017 Sep;61(9). doi: 10.1002/mnfr.201600842. Epub 2017 Mar 20.
• Results Dziedzic A, Kubina R, Kabala-Dzik A, Tanasiewicz M. Induction of Cell Cycle Arrest and Apoptotic Response of Head and Neck Squamous Carcinoma Cells (Detroit 562) by Caffeic Acid and Caffeic Acid Phenethyl Ester Derivative. Evid Based Complement Alternat Med. 2017;2017:6793456. doi: 10.1155/2017/6793456. Epub 2017 Jan 12.
• Results Sirota R, Gibson D, Kohen R. The timing of caffeic acid treatment with cisplatin determines sensitization or resistance of ovarian carcinoma cell lines. Redox Biol. 2017 Apr;11:170-175. doi: 10.1016/j.redox.2016.12.006. Epub 2016 Dec 7.

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