2. Academic Validation
  3. Flavokawain C inhibits proliferation and migration of liver cancer cells through FAK/PI3K/AKT signaling pathway

Flavokawain C inhibits proliferation and migration of liver cancer cells through FAK/PI3K/AKT signaling pathway

  • J Cancer Res Clin Oncol. 2024 Mar 9;150(3):117. doi: 10.1007/s00432-024-05639-z.
Rong Wang 1 2,  Rizhao Li 2,  Huibing Yang 2,  Xuejiao Chen 1 2,  Liangliang Wu 2,  Xiaohui Zheng 3,  Yuepeng Jin 4
Affiliations

Affiliations

  • 1 National Key Clinical Specialty (General Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China.
  • 2 Wenzhou Medical University, Wenzhou, 325000, China.
  • 3 Wenzhou Medical University, Wenzhou, 325000, China. [email protected].
  • 4 National Key Clinical Specialty (General Surgery), The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, China. [email protected].
PMID: 38460052 DOI: 10.1007/s00432-024-05639-z
Abstract

Purpose: This study investigated the potential applicability and the underlying mechanisms of flavokawain C, a natural compound derived from kava extracts, in liver Cancer treatment.

Methods: Drug distribution experiment used to demonstrate the preferential tissues enrichment of flavokawain C. Cell proliferation, Apoptosis and migration effect of flavokawain C were determined by MTT, colony formation, EdU staining, cell adhesion, transwell, flow cytometry and western blot assay. The mechanism was explored by comet assay, immunofluorescence assay, RNA-seq-based Kyoto encyclopedia of genes and genomes analysis, molecular dynamics, bioinformatics analysis and western blot assay. The Anticancer effect of flavokawain C was further confirmed by xenograft tumor model.

Results: The studies first demonstrated the preferential enrichment of flavokawain C within liver tissues in vivo. The findings demonstrated that flavokawain C significantly inhibited proliferation and migration of liver Cancer cells, induced cellular Apoptosis, and triggered intense DNA damage along with strong DNA damage response. The findings from RNA-seq-based KEGG analysis, molecular dynamics, bioinformatics analysis, and western blot assay mechanistically indicated that treatment with flavokawain C notably suppressed the FAK/PI3K/Akt signaling pathway in liver Cancer cells. This effect was attributed to the induction of gene changes and the binding of flavokawain C to the ATP sites of FAK and PI3K, resulting in the inhibition of their phosphorylation. Additionally, flavokawain C also displayed the strong capacity to inhibit Huh-7-derived xenograft tumor growth in mice with minimal adverse effects.

Conclusions: These findings identified that flavokawain C is a promising Anticancer agent for liver Cancer treatment.

Keywords

DNA damage; FAK/PI3K/AKT pathway; Flavokawain C; Liver cancer; Migration; Proliferation.

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