Flavonoids from persimmon (Diospyros kaki L.) leaves inhibit proliferation and induce apoptosis in PC-3 cells by activation of oxidative stress and mitochondrial apoptosis

Chem Biol Interact. 2017 Sep 25;275:210-217. doi: 10.1016/j.cbi.2017.07.026. Epub 2017 Aug 12.

Abstract

Persimmon (Diospyros kaki L.) leaves are extensively used in Chinese medicine and are also excellent source of dietary polyphenols. Here we investigated the antiproliferative and pro-apoptotic activity of the total flavonoids extracted from persimmon leaves (FPL) in PC-3 cells. After treating cells with different concentration of FPL, Quercetin or Rutin for 24 h, MTT and flow cytometry were used to measure the cytotoxicity, apoptotic rate and cell cycle arrest. Compared with Quercetin and Rutin, FPL showed higher cytotoxicity at 12.5 and 25 μg/ml concentrations and also presented lower IC50 in PC-3 cells. In addition, FPL induced PC-3 cells apoptosis by activation of oxidative stress, as detected by ROS, MDA, nitrite and iNOS activity, and increased mitochondrial membrane permeability. Morphological changes, inactivation of Bcl-2, upregulation of BAX, release of cytochrome c and activation of downstream apoptotic signaling in FPL-treated PC-3 cells also suggested apoptotic death. Meanwhile, FPL significantly inhibited migration of PC-3 cells. Therefore, FPL inhibited proliferation, migration and induced apoptosis of PC-3 cells by activation of oxidative stress and mitochondrial-related apoptosis.

Keywords: Apoptosis; Cytotoxicity; Flavonoids; Oxidative stress; Persimmon leaves; Prostate cancer.

MeSH terms

  • Apoptosis / drug effects*
  • Cell Cycle Checkpoints / drug effects
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects*
  • Cytochromes c / metabolism
  • Diospyros / chemistry*
  • Diospyros / metabolism
  • Flavonoids / chemistry
  • Flavonoids / isolation & purification
  • Flavonoids / pharmacology*
  • Humans
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / metabolism
  • Oxidative Stress / drug effects*
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Plant Leaves / chemistry
  • Plant Leaves / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Reactive Oxygen Species / metabolism
  • Up-Regulation / drug effects
  • bcl-2-Associated X Protein / metabolism

Substances

  • Flavonoids
  • Plant Extracts
  • Proto-Oncogene Proteins c-bcl-2
  • Reactive Oxygen Species
  • bcl-2-Associated X Protein
  • Nitric Oxide
  • Cytochromes c
  • Nitric Oxide Synthase Type II