Fatty acid synthase (FASN) is highly expressed in
breast carcinomas to support their continuous growth and proliferation, but has low expression level in normal tissues. Considerable interest has been developed in searching for novel FASN inhibitors as a therapeutic target for
breast cancer. In present study,
amentoflavone was isolated from Selaginella tamariscina, a
traditional oriental medicine that has been used to treat
cancer for many years, and was found to significantly inhibit the in vitro enzymatic activity of FASN at concentrations above 50 microM.
Amentoflavone was also found to decrease
fatty acid synthesis by the reduction of [(3)H]
acetyl-CoA incorporation into
lipids in FASN-overexpressed SK-BR-3 human
breast cancer cells. Furthermore, this study showed that
amentoflavone, at a concentration greater than 75 microM, increased the cleavage-activity of
caspase-3 and
poly (ADP-ribose) polymerase (PARP), and administration of pan-
caspase inhibitor
Z-VAD-FMK completely rescued the SK-BR-3 cells from PARP cleavages. The sequential internucleosomal DNA fragmentation in SK-BR-3 cells was observed at a concentration of 100 microM. A decrease in
breast cancer cell growth was observed in SK-BR-3 cells at 12 and 24 h post treatment with 100 microM of
amentoflavone, followed by a dramatic suppression after 48 h. The inhibition of
cancer-growth by
amentoflavone was dose-dependent, showing a slight reduction at 50 microM and significant reduction at concentrations of 75 and 100 microM. FASN-nonexpressed NIH-3T3 normal cell growth was not decreased by
amentoflavone-treatment, both in time- and dose-dependent manners. These data provide evidence that
amentoflavone isolated from S. tamariscina induced
breast cancer apoptosis through blockade of
fatty acid synthesis.