Evaluation of Therapeutic Potential of Phenoxodiol, a Novel Isoflavone Analog, in Renal Cancer Cells

Anticancer Res. 2018 Oct;38(10):5709-5716. doi: 10.21873/anticanres.12908.

Abstract

Background/aim: In the present study, the antineoplastic activity and mechanism of action of phenoxodiol, a novel isoflavone analog, was investigated in renal cancer cells.

Materials and methods: A panel of renal cancer cells (769-P, 786-O, Caki-2) was treated with phenoxodiol in vitro, and the efficacy of treatment was evaluated.

Results: MTS assay results showed that phenoxodiol decreased renal cancer viability in a dose-dependent manner. In addition, it inhibited colony formation significantly and perturbed the cell cycle. Treatment with phenoxodiol increased the number of annexin-V-positive cells as well as the expression of cleaved poly ADP ribose polymerase, demonstrating that phenoxodiol induced apoptosis in renal cancer cells. Phenoxodiol also inhibited Akt pathway via dephosphorylation of Akt.

Conclusion: Phenoxodiol inhibited Akt pathway and induced apoptosis of renal cancer cells. The present study provides a theoretical basis for future development of a novel therapy effective against renal cancer.

Keywords: Akt; Phenoxodiol; c-FLIP; renal cancer.

Publication types

  • Evaluation Study

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • CASP8 and FADD-Like Apoptosis Regulating Protein / metabolism
  • Carcinoma, Renal Cell / drug therapy
  • Carcinoma, Renal Cell / metabolism
  • Carcinoma, Renal Cell / pathology*
  • Cell Proliferation / drug effects*
  • Gene Expression Regulation, Neoplastic / drug effects*
  • Humans
  • Isoflavones / pharmacology*
  • Kidney Neoplasms / drug therapy
  • Kidney Neoplasms / metabolism
  • Kidney Neoplasms / pathology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • CASP8 and FADD-Like Apoptosis Regulating Protein
  • CFLAR protein, human
  • Isoflavones
  • phenoxodiol
  • AKT1 protein, human
  • Proto-Oncogene Proteins c-akt