Gypensapogenin H suppresses tumor growth and cell migration in triple-negative breast cancer by regulating PI3K/AKT/NF-κB/MMP-9 signaling pathway

Bioorg Chem. 2022 Sep:126:105913. doi: 10.1016/j.bioorg.2022.105913. Epub 2022 May 26.

Abstract

Due to its aggressiveness and high metastasis rates, triple-negative breast cancer (TNBC) is a ubiquitous and deadly disease for the majority of women globally. Gypensapogenin H (GH) is a novel dammarane-type triterpene isolated from hydrolyzate of total saponins from Gynostemma pentaphyllum. Our previous work demonstrated that GH promoted apoptosis in TNBC. In the present study, xenograft TNBC models (xenotransplantation of MDA-MB-231 cells in nude mice) were used to evaluate the efficacy of GH in vivo. We preliminarily predicted the mechanism of GH inhibiting breast cancer tumors at the gene level through transcriptome screening. Through western blot analysis of tumor tissue, we found that GH could inhibit tumor proliferation and migration by regulating the PI3K/AKT/NF-κB/MMP-9 signaling pathway in vivo. We also analyzedthe results at the cell level in vitro, which were consistent with those in vivo. In summary, GH inhibited TNBC growth in vivo and suppressed TNBC cell migration in vitro. Our findings could help understand the mechanism of action of GH and suggest that GH would be a promising agent for TNBC therapy.

Keywords: Gypensapogenin H,; PI3K/AKT/NF-κB/MMP-9 signaling pathway; Triple-Negative Breast Cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Female
  • Humans
  • Matrix Metalloproteinase 9
  • Mice
  • Mice, Nude
  • NF-kappa B / metabolism
  • Phosphatidylinositol 3-Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Saponins* / pharmacology
  • Saponins* / therapeutic use
  • Signal Transduction
  • Triple Negative Breast Neoplasms* / metabolism

Substances

  • NF-kappa B
  • Saponins
  • gypensapogenin H
  • Proto-Oncogene Proteins c-akt
  • Matrix Metalloproteinase 9