The synergistic effect of 2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-glucoside combined with Adriamycin on MCF-7 breast cancer cells

Drug Des Devel Ther. 2018 Nov 30:12:4083-4094. doi: 10.2147/DDDT.S186028. eCollection 2018.

Abstract

Objective: Breast cancer has been reported to be a serious disease and a threat to women's health. 2,3,5,4'-Tetrahydroxystilbene-2-O-β-d-glucoside (THSG) is a bioactive natural compound originating from Polygonum multiflorum Thunb., which has been shown to possess anti-inflammatory and antitumor properties. Adriamycin (ADM) is a chemotherapy agent used in tumor therapy that is limited by its side effects. However, little is known about the synergistic effect of THSG combined with ADM on breast cancer. This study seeks to investigate the effects of the combination of THSG plus ADM on MCF-7 breast cancer cells and to test the mechanisms involved.

Materials and methods: MTT assay was detected to determine cell viability. Furthermore, cell apoptosis was tested by flow cytometry and TUNEL assay. In addition, protein expression was measured by Western blot analysis.

Results: The individual treatment of THSG and ADM induced cell injury. Moreover, cotreatment further increased it, which the effect may be associated with the elevation of the apoptotic-related protein expression such as Bax/Bcl-2 and cleaved caspase-3/caspase-3. Lastly, our results also show the reduction of vascular endothelial growth factor/phosphatidylinositol 3-kinase/Akt protein expression in the individual or synergistic treatment.

Conclusion: Taken together, cotreatment of THSG and ADM may exert a synergistic reduction of cell injury via the inhibition of vascular endothelial growth factor/phosphatidylinositol 3-kinase/Akt pathway. Thus, THSG might possess potent anti-breast cancer effect with ADM.

Keywords: ADM; THSG; VEGF/PI3K/Akt; apoptosis; breast cancer; synergistic effect.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis / drug effects
  • Apoptosis Regulatory Proteins / metabolism
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / metabolism
  • Breast Neoplasms / pathology
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Doxorubicin / pharmacology*
  • Drug Synergism
  • Female
  • Glucosides / pharmacology*
  • Humans
  • MCF-7 Cells
  • Phosphatidylinositol 3-Kinase / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction / drug effects
  • Stilbenes / pharmacology*
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • Apoptosis Regulatory Proteins
  • Glucosides
  • Stilbenes
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • 2,3,5,4'-tetrahydroxystilbene 2-O-glucopyranoside
  • Doxorubicin
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt