Baicalein is a
flavonoid, known to have anti-inflammatory and anti-
cancer effects. As an
aryl hydrocarbon receptor (AhR)
ligand,
baicalein at high concentrations blocks AhR-mediated
dioxin toxicity. Because AhR had been reported to play a role in regulating the cell cycle, we suspected that the anti-
cancer effect of
baicalein is associated with AhR. This study investigated the molecular mechanism involved in the anti-
cancer effect of
baicalein in
oral cancer cells HSC-3, including whether such effect would be AhR-mediated. Results revealed that
baicalein inhibited cell proliferation and increased AhR activity in a dose-dependent manner. Cell cycle was arrested at the G1 phase and the expression of CDK4,
cyclin D1, and phosphorylated
retinoblastoma (pRb) was decreased. When the AhR was suppressed by
siRNA, the reduction of pRb was partially reversed, accompanied by a decrease of cell population at G1 phase and an increase at S phase, while the reduction of
cyclin D1 and CDK4 did not change. This finding suggests that the
baicalein activation of AhR is indeed associated with the reduction of pRb, but is independent of the reduction of
cyclin D1 and CDK4. When cells were pre-treated with LiCl, the inhibitor of GSK-3β, the decrease of
cyclin D1 was blocked and the reduction of pRb was recovered. The data indicates that in HSC-3 the reduction of pRb is both mediated by
baicalein through activation of AhR and facilitation of
cyclin D1 degradation, which causes cell cycle arrest at the G1 phase, and results in the inhibition of cell proliferation.