Polyphyllin VII Promotes Apoptosis in Breast Cancer by Inhibiting MAPK/ERK Signaling Pathway through Downregulation of SOS1

Am J Chin Med. 2024;52(3):885-904. doi: 10.1142/S0192415X24500368. Epub 2024 May 8.

Abstract

Polyphyllin VII is a biologically active herbal monomer extracted from the traditional Chinese herbal medicine Chonglou. Many studies have demonstrated the anticancer activity of polyphyllin VII against various types of cancers, such as colon, liver, and lung cancer, but its effect on breast cancer has not been elucidated. In this study, we demonstrate that polyphyllin VII inhibited proliferation, increased production of intracellular reactive oxygen species, and decreased mitochondrial membrane potential in breast cancer cells. Notably, polyphyllin VII also induced apoptosis via the mitochondrial pathway. Transcriptome sequencing was used to analyze the targets of PPVII in regulating breast cancer cells. Mechanistic studies showed that polyphyllin VII downregulated Son of Sevenless1 (SOS1) and inhibited the MAPK/ERK pathway. Furthermore, PPVII exerted strong antitumor effects in vivo in nude mice injected with breast cancer cells. Our results suggest that PPVII may promote apoptosis through regulating the SOS1/MAPK/ERK pathway, making it a possible candidate target for the treatment of breast cancer.

Keywords: Breast Cancer; Cell Apoptosis; MAPK/ERK Signaling Pathway; Polyphyllin VII; SOS1.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis* / drug effects
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / genetics
  • Breast Neoplasms* / metabolism
  • Breast Neoplasms* / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Down-Regulation* / drug effects
  • Drugs, Chinese Herbal / pharmacology
  • Female
  • Humans
  • MAP Kinase Signaling System* / drug effects
  • Membrane Potential, Mitochondrial / drug effects
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Phytotherapy
  • Reactive Oxygen Species / metabolism
  • SOS1 Protein* / genetics
  • SOS1 Protein* / metabolism
  • Saponins / pharmacology
  • Saponins / therapeutic use

Substances

  • polyphyllin VII
  • SOS1 Protein
  • Saponins
  • Reactive Oxygen Species
  • Drugs, Chinese Herbal
  • Antineoplastic Agents, Phytogenic