Int J Biol Sci 2022; 18(7):2759-2774. doi:10.7150/ijbs.70567 This issue

Research Paper

Alizarin, a nature compound, inhibits the growth of pancreatic cancer cells by abrogating NF-κB activation

Zihang Xu1#, Yifei Hou1#, Chunpu Zou1, Haibin Liang2, Jiasheng Mu2, Xiaoning Jiao1, Yangzhuangzhuang Zhu1, Lin Su1, Mingxi Liu1, Xiao Chen1, Chunmei Qian3, Xiandan Zhu3, Wei Gong2, Qian Dong2✉, Fei Zhang2✉

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
# These authors contributed equally to this work.

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Citation:
Xu Z, Hou Y, Zou C, Liang H, Mu J, Jiao X, Zhu Y, Su L, Liu M, Chen X, Qian C, Zhu X, Gong W, Dong Q, Zhang F. Alizarin, a nature compound, inhibits the growth of pancreatic cancer cells by abrogating NF-κB activation. Int J Biol Sci 2022; 18(7):2759-2774. doi:10.7150/ijbs.70567. Available from https://www.ijbs.com/v18p2759.htm

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Abstract

Graphic 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.

Keywords: Nature compound, Alizarin, Pancreatic cancer, NF-κB signal, Gemcitabine