Sasanquasaponin inhibited epithelial to mesenchymal transition in prostate cancer by regulating the PI3K/Akt/mTOR and Smad pathways

Pharm Biol. 2022 Dec;60(1):1865-1875. doi: 10.1080/13880209.2022.2123931.

Abstract

Context: Sasanquasaponin (SQS) is a commonly used traditional Chinese medicine proved to have a wide range of pharmacological functions.

Objective: The objective of this study is to explore the effect and underlying mechanism of SQS in the treatment of prostate cancer (PC).

Materials and methods: PC cell lines (22Rv1 and PC-3) were treated with SQS (0, 0.5, 1, 2, and 4 μM) for 12 or 24 h. The viability of cells was evaluated, while the mRNA and protein levels of epithelial to mesenchymal transition (EMT)-related genes in PC cell lines were measured (Groups: Control, TGF-β1, TNF-α, TGF-β1 + TNF-α, and TGF-β1 + TNF-α + SQS). The migration and invasion abilities of PC cell lines were evaluated (Groups: Control, SQS). Finally, the antitumour effect of SQS (25, 50,100, and 200 mg/kg) in BALB/c nude mice (6 weeks, 18-20 g) was evaluated (Groups: Control, Vehicle, 25, 50,100, and 200 mg/kg SQS). The study duration was 1 month.

Results: SQS inhibited the viability and the number of colonies of 22Rv1 or PC-3 cells. The IC50 of SQS of 12 and 24 h in these two cells was 3.25, 1.82, 4.76, and 4.70 μM, respectively. SQS inhibited the adhesion, migration, and invasion of PC cells. It also inhibited the expression of EMT-related markers of PC cells. The PI3K/Akt/mTOR and Smad2/3 signalling pathways were activated in the process of EMT, and SQS could significantly reduce the activation of the PI3K/Akt/mTOR and Smad2/3 pathways. Finally, SQS inhibited the growth of xenograft tumours in vivo.

Conclusions: SQS inhibited EMT in PC by regulating the PI3K/Akt/mTOR and Smad pathways.

Keywords: Traditional Chinese medicine; adhesion; invasion; migration; signalling pathway.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Movement
  • Epithelial-Mesenchymal Transition*
  • Humans
  • Male
  • Mice
  • Mice, Nude
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prostatic Neoplasms* / drug therapy
  • Proto-Oncogene Proteins c-akt / metabolism
  • RNA, Messenger
  • Saponins
  • Smad Proteins / metabolism
  • TOR Serine-Threonine Kinases / metabolism
  • Transforming Growth Factor beta1 / metabolism
  • Tumor Necrosis Factor-alpha / pharmacology

Substances

  • 22-O-angeloylcamelliagenin C-3-O-(glucopyranosyl-1-2)(glucopyranosyl-1-2-O-arabinopyranosyl-1-3-)glucopyranosiduronic acid
  • RNA, Messenger
  • Saponins
  • Smad Proteins
  • Transforming Growth Factor beta1
  • Tumor Necrosis Factor-alpha
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases

Grants and funding

This work was supported by the Interdisciplinary Program of Shanghai Jiao Tong University (No. YG2022ZD011) and the National Natural Science Foundation of China (No. 82072846, M-0171).