Quercitrin, glycosylated form of
flavonoid compounds, is widely distributed in nature. Extensive studies have demonstrated that
quercitrin exhibits strong
antioxidant and anti-carcinogenic activities. However, the molecular mechanism is poorly understood. The present study examines the effects of
quercitrin on
tumor promotion in mouse JB6 cells, a validated model for screening
cancer chemopreventive agents and elucidating the molecular mechanisms.
Quercitrin blocked TPA-induced neoplastic transformation in JB6 P+ cells. Pretreatment of JB6 cells with
quercitrin down-regulated transactivation of
AP-1 and
NF-kappaB induced by UVB or TPA. In the skin of AP-1-luciferase transgenic mice, topical treatment of the mouse with
quercitrin markedly blocked the TPA-induced
AP-1 transactivation. Further studies indicated that these inhibitory actions appear to be mediated through the inhibition of MAPKs phosphorylation, including ERKs, p38
kinase, and JNKs. In addition,
quercitrin stimulated the activation of NF-E2-related factor (Nrf2) and GST ARE-
luciferase activity. Comet assays showed that
quercitrin could block DNA damage induced by UVB. To our knowledge, these results provide the first evidence that
quercitrin contributes to the inhibition of neoplastic transformation by blocking activation of the MAPK pathway and stimulation of cellular protection signaling. Moreover, to our knowledge, these findings provide the first molecular basis for the anti-carcinogenic action of
quercitrin.