Probing the Molecular Mechanisms Governing the Oncolytic Activity of Paeonia suffruticosa on Triple-negative Breast Cancer Cells In Vitro

Anticancer Res. 2017 Sep;37(9):4813-4819. doi: 10.21873/anticanres.11888.

Abstract

Background/aim: Extracts of Paeonia suffruticosa are traditionally used in Chinese medicine to increase blood flow. Recently, this extract has been shown to possess anti-tumor and anti-inflammatory properties, though this mechanism remains unknown. In the current work, we prepared extracts of P. suffruticosa and analyzed their effects on MDA-MB-231 triple-negative breast cancer cells.

Materials and methods: Varying concentrations of an aqueous extract of P. suffruticosa was administered to MDA-MB-231. An MTS assay was used to determine the cell viability. Cytokine production was investigated through enzyme-linked immunosorbent assay (ELISA). Caspase-Glo assays were performed to measure caspase 3/7, 8 and 9 to analyze anti-apoptotic effects.

Results: MTS assay for cell viability revealed that the extract increased viability at low concentrations (0.6 mg/ml) and decreased viability observed at concentrations ≥2.5 mg/ml (p<0.01). ELISA for IL-6, IL-2, and TNF-alpha revealed a biphasic dose-response inversely related to viability (p<0.05). IL-24 expression also increased at 2.5 mg/ml and 4.0 mg/ml (p<0.05). Bax levels remained relatively constant while Bcl-2 decreased significantly in all concentrations (p<0.01). Small decreases in Fas ligand levels was observed in parallel with a lack of increase in caspase-8 activity. Most notable was that while 4mg/ml of P. suffruticosa extract reduced MDA-MB-231 viability by >60% (p<0.01), the same concentration reduced the viability of non-transformed HaCat cells by ~8% (p>0.05), suggesting a selective oncolytic effect.

Conclusion: P. suffruticosa extract has the ability to modulate the production of several tumor suppressive cytokines, induce intrinsic apoptosis and has the capability of reducing cancer burden while sparing healthy tissue.

Keywords: Apoptosis; Paeonia suffruticosa; cytokine; drug discovery; triple-negative breast cancer.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Antineoplastic Agents / therapeutic use*
  • Apoptosis / drug effects
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cytokines / biosynthesis
  • Female
  • Humans
  • Paeonia
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use*
  • Triple Negative Breast Neoplasms / enzymology
  • Triple Negative Breast Neoplasms / pathology*

Substances

  • Antineoplastic Agents
  • Cytokines
  • Plant Extracts
  • Caspases