A biflavonoid-rich extract from Selaginella moellendorffii Hieron. induces apoptosis via STAT3 and Akt/NF-κB signalling pathways in laryngeal carcinoma

J Cell Mol Med. 2020 Oct;24(20):11922-11935. doi: 10.1111/jcmm.15812. Epub 2020 Sep 1.

Abstract

Selaginella moellendorffii Hieron. (SM), a perennial evergreen plant, has been used in the treatment of acute infectious hepatitis, thoracic and hypochondriac lumbar contusions, systemic oedema and thrombocytopaenia. However, the role of a biflavonoid-rich extract from SM (SM-BFRE) in anti-larynx cancer has rarely been reported. In this study, the in vitro and in vivo anti-laryngeal cancer activity and potential mechanisms of SM-BFRE were investigated. An off-line semipreparative liquid chromatography-nuclear magnetic resonance protocol was carried out to determine six biflavonoids from SM-BFRE. In vitro, MTT assay revealed that SM-BFRE inhibited the proliferation of laryngeal carcinoma cells. A wound healing assay indicated that SM-BFRE suppressed the migration of laryngeal cancer cells. Hoechst 33 258 and Annexin V-FITC/PI double staining assays were performed and verified that SM-BFRE induced apoptosis in laryngeal carcinoma cells. The Hep-2 bearing nude mouse model confirmed that SM-BFRE also exhibited anticancer effect in vivo. In addition, Western blot analysis demonstrated that SM-BFRE exerted its anti-laryngeal cancer effect by activating the mitochondrial apoptotic pathway and inhibiting STAT3 and Akt/NF-κB signalling pathways. All results suggested that SM-BFRE could be considered as a potential chemotherapeutic drug for laryngeal cancer.

Keywords: Akt/NF-κB; STAT3; Selaginella moellendorffii Hieron.; apoptosis; biflavonoid-rich extract; laryngeal carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Biflavonoids / chemistry
  • Biflavonoids / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Female
  • Humans
  • Laryngeal Neoplasms / metabolism*
  • Laryngeal Neoplasms / pathology*
  • Mice, Inbred BALB C
  • Mice, Nude
  • Models, Biological
  • NF-kappa B / metabolism*
  • Neoplasm Transplantation
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • STAT3 Transcription Factor / metabolism*
  • Selaginellaceae / chemistry*
  • Signal Transduction / drug effects

Substances

  • Biflavonoids
  • NF-kappa B
  • Plant Extracts
  • STAT3 Transcription Factor
  • Proto-Oncogene Proteins c-akt