BZL101 is an aqueous extract from the Scutellaria barbata plant shown to have anticancer properties in a variety of human
cancers. In order to determine its efficacy on human reproductive
cancers, we assessed the responses of two human
breast cancer cell lines,
estrogen sensitive MCF7 and
estrogen insensitive MDA-MB-231, and of two human
prostate cancer cell lines,
androgen sensitive LNCaP and
androgen insensitive PC3 which are human cell lines that represent early and late stage reproductive
cancers.
BZL101 inhibited reproductive
cancer growth in all cell lines by regulating expression levels of key cell cycle components that differ with respect to the
cancer cell phenotypes. In early stage
estrogen sensitive MCF7 cells,
BZL101 induced a G₁ cell cycle arrest and ablated expression of key G₁ cell cycle regulators
Cyclin D1, CDK2 and CDK4, as well as
growth factor stimulatory pathways and
estrogen receptor-α expression. Transfection of
luciferase reporter plasmids revealed that the loss of CDK2, CDK4 and
estrogen receptor-α transcript expression resulted from the BZL-dependent ablation of promoter activities.
BZL101 growth arrests early stage
androgen sensitive LNCaP cells in the G₂/M phase with corresponding decreases in
Cyclin B1, CDK1 and
androgen receptor expression. In late stage
hormone insensitive breast (MDA-MB-231) and prostate (PC3)
cancer cells,
BZL101 induced an S phase arrest with corresponding ablations in
Cyclin A2 and CDK2 expression. Our results demonstrate that
BZL101 exerts phenotype specific anti-proliferative gene expression responses in human breast and
prostate cancer cells, which will be valuable in the potential development of BZL-based therapeutic strategies for human reproductive
cancers.