Alizarin,a nature compound,inhibits the growth of pancreatic cancer cells by abrogating NF-κB activation |
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Authors: | Zihang Xu Yifei Hou Chunpu Zou Haibin Liang Jiasheng Mu Xiaoning Jiao Yangzhuangzhuang Zhu Lin Su Mingxi Liu Xiao Chen Chunmei Qian Xiandan Zhu Wei Gong Qian Dong Fei Zhang |
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Affiliation: | 1.Shanghai Key Laboratory of Health Identification and Assessment, School of Basic Medical Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.;2.Department of General Surgery, Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200092, China;3.Experimental Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China |
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Abstract: | The current performance of nature compounds in antitumor field is gradually attracted more and more attention, we discovered a nature active ingredient alizarin possess potent natural reductive NF-κB activity to against pancreatic cancer. However, the preclinical pharmacology and therapeutic effect, and the underlying mechanisms of alizarin in inhibiting pancreatic cancer are still unclear. After high-throughput screening, this is the first report that alizarin can induce a potent inhibitory effect against pancreatic cancer cells. Alizarin induced cell cycle arrest and promoted cell apoptosis by inhibiting TNF-α-stimulated NF-κB activity and nuclear translocation, and inactivated its related TNF-α-TAK1-NF-κB signaling cascade followed by downregulation of NF-κB target genes involved in cell apoptosis (Bcl-2, Bcl-xL, XIAP) and in the cell cycle and growth (cyclin D, c-myc). Due to the abrogation of NF-κB activity, combination of alizarin and gemcitabine exerted a better inhibitory effect on pancreatic cancer. In summary, natural component alizarin, inhibited cell proliferation and induced apoptosis in vitro and in vivo through targeting of the NF-κB signaling cascade with minimal toxicity, which combine with gemcitabine, can significantly enhance the antitumor capability, playing a synergistic effect. Therefore, alizarin may play a role in reversing gemcitabine resistance caused by overactivated NF-κB in clinical application in the future. |
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Keywords: | Nature compound, Alizarin, Pancreatic cancer, NF-κ B signal, Gemcitabine |
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