The ethanol extraction of prepared Psoralea corylifolia induces apoptosis and autophagy and alteres genes expression assayed by cDNA microarray in human prostate cancer PC-3 cells

Environ Toxicol. 2018 Jul;33(7):770-788. doi: 10.1002/tox.22564. Epub 2018 Apr 18.

Abstract

Prostate cancer is the most common male reproductive system cancer. The prevalence of prostate cancer in Europe and the United States is higher than that in the Asian region. However, the treatment of prostate cancer remains unsatisfactory. Psoralea corylifolia has been used to cure this disease as Chinese medicine in the Asian region. In this study, we analyzed the components of ethanol extraction of unprepared and prepared P. corylifolia by HPLC. Psoralen and isopsoralen content from the prepared P. corylifolia is twofold higher than that from unprepared, so we use the prepared extraction in this study. However, the effects of the ethanol extraction of P. corylifolia (PCE) on PC-3 human prostate cancer cells remain unclear. PC-3 cells were treated with PCE for different time periods and cells were examined for cell morphological change and total viable cells by using contrast phase microscopy and flow cytometer, respectively. Results indicated that PCE induced cell morphological changes and cytotoxic effect in PC-3 cells in dose-dependent manners. PCE induced chromatin condensation of PC-3 cells dose-dependently. PCE also induced apoptosis and autophagy in PC-3 by western blotting and acridine orange (AO) staining, respectively. Furthermore, a complementary DNA microarray analysis demonstrated that PCE treatment led to 944 genes upregulation and 872 genes downregulation. For example, the DNA damage-associated gene DNA-damage-inducible transcript 3 (DDIT 3) had a 62.1-fold upregulation and CDK1 2.68-fold downregulation. The differential genes were classified according to the Gene Ontology. Furthermore, GeneGo software was used for the key genes involved and their possible interaction pathways. Those genes were affected by P. corylifolia, which provided information for the understanding of the antiprostate cancer mechanism at the genetic level and provide additional targets for the treatments of human prostate cancer.

Keywords: PC-3; Psoralea corylifolia; apoptosis; autophagy; prostate cancer.

MeSH terms

  • Apoptosis / drug effects*
  • Autophagy / drug effects*
  • CDC2 Protein Kinase / genetics
  • CDC2 Protein Kinase / metabolism
  • Cell Line, Tumor
  • Down-Regulation / drug effects
  • Ethanol / chemistry
  • Ficusin / chemistry
  • Ficusin / isolation & purification
  • Ficusin / pharmacology
  • Furocoumarins / chemistry
  • Furocoumarins / isolation & purification
  • Furocoumarins / pharmacology
  • Humans
  • Male
  • Oligonucleotide Array Sequence Analysis
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Psoralea / chemistry*
  • Psoralea / metabolism
  • Transcription Factor CHOP / genetics
  • Transcription Factor CHOP / metabolism
  • Up-Regulation / drug effects

Substances

  • Furocoumarins
  • Plant Extracts
  • Transcription Factor CHOP
  • Ethanol
  • angelicin
  • CDC2 Protein Kinase
  • Ficusin