Sorghum 3-Deoxyanthocyanins Possess Strong Phase II Enzyme Inducer Activity and Cancer Cell Growth Inhibition Properties

3-Deoxyanthoxyanins (3-DXA) possess unique chemical and biochemical properties and may be useful in helping reduce incidence of gastrointestinal cancer. This study tested sorghum extracts rich in 3-DXA as well as isolated and synthetic 3-DXA for potential to induce activity of phase II enzymes in murine hepatoma cells using the NAD(P)H:quinone oxidoreductase (NQO) assay and to inhibit proliferation of the HT-29 human colon cancer cells using MTT and PicoGreen assays. Crude black sorghum extract that contained high levels of methoxylated 3-DXA was a strong inducer of NQO activity (3.0 times at 50 mu g/mL), compared to red or white sorghum extracts with low or no methoxylated 3-DXA (1.6 times at 200 mu g/mL). All sorghum extracts had strong antiproliferative activity against HT-29 cells after 48 h of incubation (IC50 = 180-557 mu g/mL). Among isolated fractions, nonmethoxylated 3-DXA were very effective against HT-29 cell growth (IC50 = 44-68 mu M at 48 h), but were noninducers of NQO. On the other hand, the methoxylated 3-DXA had both strong antiproliferative activity (IC50 < 1.5-53 mu M) and NQO inducer activity (2-3.7 times). Dimethoxylated 3-DXA were more potent than monomethoxylated analogues. Methoxylation of 3-DXA is essential for NQO activity and also enhances tumor cell growth inhibition.