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.