Alizarin, a nature compound, inhibits the growth of pancreatic cancer cells by abrogating NF-κB activation
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
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-B 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--stimulated NF-B activity and nuclear translocation, and inactivated its related TNF--TAK1-NF-B signaling cascade followed by downregulation of NF-B 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-B 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-B 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-B in clinical application in the future.