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

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.
AuthorsHongyan Tan, Meng Zhang, Lei Xu, Xiaoshu Zhang, Yuqing Zhao
JournalBioorganic chemistry (Bioorg Chem) Vol. 126 Pg. 105913 (09 2022) ISSN: 1090-2120 [Electronic] United States
PMID35671647 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
CopyrightCopyright © 2022. Published by Elsevier Inc.
Chemical References
  • NF-kappa B
  • Saponins
  • gypensapogenin H
  • Proto-Oncogene Proteins c-akt
  • Matrix Metalloproteinase 9
Topics
  • 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, therapeutic use)
  • Signal Transduction
  • Triple Negative Breast Neoplasms (metabolism)

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