Scutellarin inhibits the invasive potential of malignant melanoma cells through the suppression epithelial-mesenchymal transition and angiogenesis via the PI3K/Akt/mTOR signaling pathway

Eur J Pharmacol. 2019 Sep 5:858:172463. doi: 10.1016/j.ejphar.2019.172463. Epub 2019 Jun 15.

Abstract

Malignant melanoma is the leading cause of death from skin disease, due in large part to its propensity to metastasize. Scutellarin is an active flavone extracted from traditional Chinese herb Erigeron breviscapus (Vant.) Hand. Mazz. Recent studies have reported that scutellarin can be utilized to treat various types of tumors. In this study, we investigated the effects of scutellarin on melanoma cancer cell invasive potential and the molecular mechanisms underlying these effects using A375 melanoma cells lines. The in-vitro antitumor activity of scutellarin was evaluated by CCK-8 assay, wound-healing assay, transwell assays, adhesion assays, and tube formation assays to assess the cell viability, migration, invasion, adhesion, and angiogenesis, respectively. Also, western blotting assay was used to assess the level of PI3K/Akt/mTOR signaling pathway proteins in A375 cells. We found that scutellarin significantly inhibited melanoma cell lines and HUVECs viability in a time- and concentration-dependent manners. Additionally, scutellarin effectively suppressed tumor cell migration, invasion, adhesion through the suppression of EMT and angiogenesis by inhibiting the PI3K/Akt/mTOR signaling pathway. These results indicated that scutellarin could markedly inhibit the invasive potential of melanoma cell lines by suppressing the EMT and angiogenesis through the PI3K/Akt/mTOR signaling pathway. It suggests that scutellarin might be a potential compound in malignant melanoma treatment.

Keywords: Angiogenesis; Epithelial-mesenchymal transition; Melanoma cells; PI3K/Akt/mtor pathway; Scutellarin.

MeSH terms

  • Apigenin / pharmacology*
  • Apigenin / therapeutic use
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Epithelial-Mesenchymal Transition / drug effects*
  • Glucuronates / pharmacology*
  • Glucuronates / therapeutic use
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / metabolism
  • Melanoma / blood supply
  • Melanoma / pathology*
  • Melanoma, Cutaneous Malignant
  • Neoplasm Invasiveness
  • Neovascularization, Pathologic / drug therapy*
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects*
  • Skin Neoplasms / blood supply
  • Skin Neoplasms / pathology*
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Glucuronates
  • scutellarin
  • Apigenin
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9