Modulation of bcl-2 and cytotoxicity by licochalcone-A, a novel estrogenic flavonoid

Anticancer Res. Jul-Aug 2000;20(4):2653-8.

Abstract

Herbal therapies are commonly used by patients with cancer, despite little understanding about their clinical and biological activity. We recently demonstrated that the herbal combination PC-SPES, which contains licorice root, had potent estrogenic activity in vitro, in animals, and in patients with prostate cancer. Licochalcone-A (LA) is one flavonoid extracted from licorice root with antiparasitic and anti-tumor activity, but the effect on the human estrogen receptor and mechanism of anti-tumor activity is unknown. Recent studies demonstrated that the mechanism of cytotoxic effect by some estrogens may involve modulation of the anti-apoptotic protein bcl-2. In the present study, we determined if LA had estrogenic activity, anti-tumor activity, and modulated the apoptotic protein bcl-2 in human cell lines derived from acute leukemia, breast cancer, and prostate cancer. A yeast growth-based assay under the control of the human estrogen receptor (hER) demonstrated that LA was a phytoestrogen. A cell viability assay demonstrated that LA had anti-tumor activity in all cell lines tested and enhanced the effect of paclitaxel and vinblastine chemotherapy. LA induced apoptosis in MCF-7 and HL-60 cell lines, as demonstrated by cleavage of PARP, the substrate of ICE-like proteases. Immunoblot analysis demonstrated that LA decreased the anti-apoptotic protein bcl-2 and altered the bcl-2/bax ratio in favor of apoptosis. In contrast, the parent compound chalcone or estradiol did not decrease bc1-2 expression. Therefore, these data demonstrate that LA is a phytoestrogen with anti-tumor activity and is capable of modulating bcl-2 protein expression. The modulation of bcl-2 may be dependent on specific structural differences between LA and the parent compound chalcone and independent of LA estrogenicity.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Antineoplastic Agents, Phytogenic / pharmacology*
  • Apoptosis / drug effects
  • Chalcone / analogs & derivatives*
  • Chalcone / pharmacology
  • Chalcones
  • Estrogens, Non-Steroidal / pharmacology*
  • Humans
  • Isoflavones*
  • Phytoestrogens
  • Plant Preparations
  • Proto-Oncogene Proteins / analysis
  • Proto-Oncogene Proteins c-bcl-2 / analysis*
  • Tumor Cells, Cultured
  • Yeasts / drug effects
  • bcl-2-Associated X Protein

Substances

  • Antineoplastic Agents, Phytogenic
  • BAX protein, human
  • Chalcones
  • Estrogens, Non-Steroidal
  • Isoflavones
  • Phytoestrogens
  • Plant Preparations
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-2-Associated X Protein
  • Chalcone
  • licochalcone A