Isoliquiritigenin inhibits mouse S180 tumors with a new mechanism that regulates autophagy by GSK‐3&bgr;/TNF‐&agr; pathway

Abstract In this study, the pharmacokinetic properties and stability of isoliquiritigenin (ILQ) in microsomes were evaluated. The data showed ILQ administrated by i.h had high absorption degree (absolute bioavailability> 90%), and strong elimination ability (average t1/2≈ 67 min). ILQ in rat tissues could reach peak at 0.25 h, and be detected in almost all tissues. In vitro, stability of ILQ in four species liver microsomes were rat > beagle dog > monkey > human > mouse. On the basis of pharmacokinetic (PK) profiles, mechanism of ILQ against S180 was explored. ILQ could not inhibit S180 growth directly in vitro. However, ILQ extremely prohibited S180 tumor volume in vivo. And when TNF‐&agr; in NK cells was knocked down by siRNA, ILQ had no inhibiting effect on S180 tumor. ILQ enhanced TNF‐&agr; expression in NK cells by FCM detection. Autophagy‐associated proteins LC3‐II, Beclin‐1, ATG‐7 were elevated in S180 cells co‐cultured with ILQ treating NK cells. When TNF‐&agr; was knocked down by siRNA, ILQ could not induce autophagy in S180 tumors. In the NK cells of osteosarcoma patients, TNF‐&agr; was negatively correlated with GSK‐3&bgr; by ELISA detection. ILQ could inhibit GSK‐3&bgr; expression and further increased p65 and c‐Rel expression in NK cells. When GSK‐3&bgr; was knocked down by siRNA, ILQ did not affect p65 and c‐Rel expression. ILQ directly inhibited GSK‐3&bgr; and then activated the NF‐&kgr;B pathway to enhance TNF‐&agr; expression in NK cells, which could induce autophagy in sarcomas. The present study supplied a new mechanism for ILQ against tumors. Graphical abstract Figure. No caption available.

• Publication year

  2018

• Venue

  European Journal of Pharmacology

• Publication date

  2018-11-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/j.ejphar.2018.08.033PMID 30171855
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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