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

Zihang Xu^1#, Yifei Hou^1#, Chunpu Zou¹, Haibin Liang², Jiasheng Mu², Xiaoning Jiao¹, Yangzhuangzhuang Zhu¹, Lin Su¹, Mingxi Liu¹, Xiao Chen¹, Chunmei Qian³, Xiandan Zhu³, Wei Gong², Qian Dong^2✉, Fei Zhang^2✉

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.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

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

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