Polyphenols purified from the Brazilian aroeira plant (Schinus terebinthifolius, Raddi) induce apoptotic and autophagic cell death of DU145 cells

Anticancer Res. 2006 Jan-Feb;26(1A):379-87.

Abstract

Polyphenols extracted from many plants have shown antiproliferative and antitumor activities in a wide range of carcinogenesis models. The antiproliferative effects of polyphenols purified from the Brazilian aroeira plant (Schinus terebinthifolius, Raddi) were investigated on the androgen-insensitive DU145 human prostatic carcinoma cell line. A F3 fraction purified from leaf extract inhibited the DU145 cell proliferation more than 30-fold compared to the crude extract. By flow cytometric analysis, the polyphenol fraction was demonstrated to induce G0/G1 cell growth arrest and cell apoptosis. This apoptosis was evidenced by caspase 3 stimulation in F3-treated cells as compared to crude extract treated cells. The acid phosphatase activity of lysosomes was strongly activated in the lysosomal fraction of the F3-treated DU145 cells. This lysosomal activation, together with the appearance of autophagic vacuoles, suggests that "type 2 physiological cell death" was also involved in this antiproliferative effect. HPLC analysis of this F3 fraction showed 18 different subfractions. Among these subfractions, F3-3, F3-7 and F3-13 strongly inhibited DU145 cell proliferation in a dose-dependent manner. However, the nature of these polyphenols remains unknown since only one (Isoquercitrin) of the tested pure polyphenols co-migrated with F3-13. Since lysosomotropic drugs are considered as possible regulators of lysosome activity, aroeira polyphenols could target lysosomes of prostatic cancer cells to induce autophagic cell death.

MeSH terms

  • Anacardiaceae / chemistry*
  • Apoptosis / drug effects*
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Flow Cytometry
  • Humans
  • Inhibitory Concentration 50
  • Lysosomes / drug effects
  • Lysosomes / metabolism
  • Male
  • Neoplasms, Hormone-Dependent / drug therapy
  • Neoplasms, Hormone-Dependent / pathology
  • Phenols / isolation & purification
  • Phenols / pharmacology*
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / pathology

Substances

  • Phenols