Biphenolic components in Magnolia obovata including
magnolol and
honokiol have shown several pharmacological activities such as anti-
tumor,
anti-oxidant and anti-inflammatory effects. Previously in cultured macrophage Raw264.7 cells and fibroblast, we found that
obovatol, an active compound isolated from M. obovata inhibited
NF-kappaB activity which has been known to be a significant transcriptional factor to control of
cancer cell growth. We investigated here whether
obovatol could inhibit
NF-kappaB activity, and thereby inhibit
cancer cell growth in prostate (LNCaP and PC-3) and
colon cancer (SW620 and HCT116) cells. Treatment of
obovatol (10, 15, 20, 25 microM) inhibits
cancer cell growth in the absence or the presence of
tumor necrosis factor-alpha (
TNF-alpha , 10 ng/ml) and tetradecanoyl
phorbol acetate (TPA 10 or 50 nM) in a concentration-dependent manner through induction of apoptotic cell death. Cytotoxic activity was not observed in normal cells with up to 50 muM
obovatol. It was also found that
obovatol inhibited
TNF-alpha and TPA-induced transcriptional and
DNA binding activities of
NF-kappaB. In further study,
obovatol decreased translocation p65 and p50 into nucleus via decrease of phosphorylation of IkappaB. Correlated well with the induction of apoptosis,
obovatol increased the expression of the apoptotic genes; Bax,
caspase-3,
caspase-9, whereas inhibited expression of anti-apoptotic genes; Bcl-2,
inhibitor of apoptosis protein (IAP-1) and X chromosome IAP (XIAP) as well as the cell proliferation marker genes; Cox-2, c-Fos, c-Jun and
cyclin D1. These results suggest that
obovatol inhibits prostate and
colon cancer cell growth via induction of apoptotic cell death, and that inhibition of
NF-kappaB may be a significant as its action mechanism.