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

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.

Alizarin as a New Activator of the Aryl Hydrocarbon Receptor Signaling Pathway

“…13 Alizarin exhibited a potent antipancreatic cancer capability by abrogating activation of nuclear factor kappa B (NF-κB) . 14 Moreover, alizarin inhibits insulin-induced fibrillation and amyloid-induced cytotoxicity. 15 On the basis of these, it was demonstrated that alizarin has several biological effects including antibacterial, antitumor, antioxidation, and anti-Alzheimer's disease.…”

The Arylamine N-Acetyltransferases as Therapeutic Targets in Metabolic Diseases Associated with Mitochondrial Dysfunction

“…Alizarin is a synthetic anthraquinone found in the roots of the madder plant. Its IC 50 for growth inhibition in a range of pancreatic cancer cells is approximately 12 µM (Xu et al, 2022), which is an order of magnitude greater than its NAT1 inhibitory concentration. This compound warrants further investigation both in vitro and in vivo as a possible selective NAT1 inhibitor.…”

Progress on the Extraction, Separation, Biological Activity, and Delivery of Natural Plant Pigments

“…Alizarin is an orange crystal or ochre yellow powder with the chemical name 1,2-dihydroxyanthraquinone. It has anticoagulants [ 58 ] and anti-cancer activities [ 89 ].…”