期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
卷 18, 期 7, 页码 2759-2774出版社
IVYSPRING INT PUBL
DOI: 10.7150/ijbs.70567
关键词
Nature compound; Alizarin; Pancreatic cancer; NE-kappa B signal; Gemcitabine
资金
- National Natural S cience Foundation of China [81804017, 81802357]
- Natural Science Foundation of Shanghai [20ZR1458500]
- Shanghai Science an d Technology Plan Project Shanghai Key Laboratory of Health Identification and Evaluation [21DZ2271000]
- Young Xinglin Scholar of S hanghai University of Traditional Chinese Medicine [A2-X200050316]
The natural compound alizarin has been found to possess potent natural reductive NF-kappa B activity, which can inhibit pancreatic cancer cells by inducing cell cycle arrest and promoting apoptosis. It can also enhance the antitumor capability when combined with gemcitabine. Alizarin may have a role in reversing gemcitabine resistance caused by overactivated NF-kappa B in clinical application in the future.
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-kappa 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-alpha-stimulated NF-kappa B activity and nuclear translocation, and inactivated its related TNF-alpha-TAK1- NF-kappa B signaling cascade followed by downregulation of NF-kappa 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-kappa 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-kappa 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-kappa B in clinical application in the future.
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