Diosmetin Induces Cell Apoptosis by Regulating CYP1A1/CYP1A2 Due to p53 Activation in HepG2 Cells

Protein Pept Lett. 2017 May 10;24(5):406-412. doi: 10.2174/0929866524666170227123557.

Abstract

It was explored that CYP1 family of cytochromes P450 were over-expressed in several types of cancer. Our study aimed to characterize anti-proliferative activity and metabolism of the natural flavonoid diosmetin in the human hepatoma cell HepG2, expressing CYP1 family. Diosinduced cell apoptosis could be reversed due to p53 blockade and the cellular P53 and CYP1A1/CYP1A2 proteins levels were examined. P53 and CYP1A1/CYP1A2 proteins were upregulated by Dios; when PFT-α was added into cells, the P53 levels were down-regulated accompanied with up-regulated CYP1A1/CYP1A2. Meanwhile, when cells were co-treated with Dios and PFT-α, P53 was down-regulated and CYP1A1/CYP1A2 up-regulated controlled with that of Dios treated cells. The data reveal the new evidence that cytochrome P450 CYP1A regulation by P53 enzyme plays an important role in Diosmetin anti-cancer activity of HepG2 cells.

Keywords: Apoptosis; CYP1A1/CYP1A2; Diosmetin; HepG2; P53; PFT-α.

MeSH terms

  • Apoptosis / drug effects*
  • Benzothiazoles / metabolism
  • Cell Proliferation / drug effects
  • Cytochrome P-450 CYP1A1 / metabolism*
  • Cytochrome P-450 CYP1A2 / metabolism*
  • Flavonoids / pharmacology*
  • Hep G2 Cells
  • Humans
  • Signal Transduction / drug effects
  • Toluene / analogs & derivatives
  • Toluene / metabolism
  • Tumor Suppressor Protein p53 / metabolism*

Substances

  • Benzothiazoles
  • Flavonoids
  • TP53 protein, human
  • Tumor Suppressor Protein p53
  • Toluene
  • pifithrin
  • CYP1A1 protein, human
  • CYP1A2 protein, human
  • Cytochrome P-450 CYP1A1
  • Cytochrome P-450 CYP1A2
  • diosmetin