Griffipavixanthone induces apoptosis of human breast cancer MCF-7 cells in vitro

Breast Cancer. 2019 Mar;26(2):190-197. doi: 10.1007/s12282-018-0912-2. Epub 2018 Sep 26.

Abstract

Background: Griffipavixanthone (GPX) is a compound extracted from Garcinia oblongifolia Champ. But, no research has yet been done about the effect of GPX on breast cancer.

Methods: We evaluated the proliferation of human breast cancer cells by CCK-8 assay and apoptosis by Annexin V (AV)-FITC and PI double staining. We used transwell assay to indicate the invasion and migration of MCF-7. To explore the molecular mechanism of GPX, we detected the mRNA and protein expression using qRT-PCR and Western blot.

Results: In this study, we evaluated if GPX could inhibit the proliferation of human breast cancer cell MCF-7 and T-47D with IC50 value of 9.64 ± 0.12 µM and 10.2 1 ± 0.38 µM at 48 h. And the IC50 value of MCF-10A is 32.11 ± 0.21 µM, which showed GPX had a tiny side effect for normal breast cells. Annexin V (AV)-FITC and PI double staining demonstrated firmly the apoptosis of MCF-7 resulting from GPX. Transwell assay indicated that GPX inhibited the invasion and migration of MCF-7. In addition, we found GPX cleaved caspase-8/9 and PARP, which play important roles in apoptotic pathway. Furthermore, through the Western blot assay, GPX increased the level of pro-apoptosis protein Bax and cytochrome C. On the contrary, GPX decreased the level of anti-apoptosis protein Bcl-2. Moreover, GPX increased the mRNA and protein expression level of p53 and its target genes, which indicated that GPX induced MCF-7 cell apoptosis by up-regulating p53 and Bax expression while suppressing Bcl-2 expression.

Conclusion: All the results showed that GPX induces MCF-7 cell apoptosis and could be considered as a potential drug for breast cancer.

Keywords: Apoptosis; Breast cancer cell MCF-7; Griffipavixanthone; P53–Bcl-2–Bax axis.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / pathology
  • Caspases / metabolism
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Drug Screening Assays, Antitumor
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Inhibitory Concentration 50
  • MCF-7 Cells
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Xanthones / pharmacology*
  • bcl-2-Associated X Protein / metabolism

Substances

  • Antineoplastic Agents, Phytogenic
  • BAX protein, human
  • BCL2 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Xanthones
  • bcl-2-Associated X Protein
  • griffipavixanthone
  • Caspases