Antiproliferative effects of citrus flavonoids on a human squamous cell carcinoma in vitro.

We examined the effects of four plant flavonoids (quercetin, taxifolin, nobiletin and tangeretin) on the in vitro growth of a human squamous cell carcinoma cell line (HTB43). Cell cultures were treated with each flavonoid (2-8 micrograms/ml) for 3-7 days. Cell viability, as determined by counting cells, correlated well with that obtained from a colorimetric assay for cellular growth utilizing 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide. The polymethoxylated flavonoids, nobiletin and tangeretin, markedly inhibited cell growth at all concentrations tested on days 5 and 7. On day 3, the inhibition observed was 70-72% at 8 micrograms/ml, while on day 5, it ranged from 61-88% at 2-4 micrograms/ml. Quercetin and taxifolin exhibited no significant inhibition at any of the concentrations tested. This difference in activity may be due to the relatively greater membrane uptake of the polymethoxylated flavonoids since methoxylation of the phenolic groups decreases hydrophilicity of the flavonoid.