Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, WV 26505, USA.
Int J Oncol. 2010 Jan;36(1):59-67.
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.
槲皮素是类黄酮化合物的糖基化形式，广泛分布于自然界。大量研究表明槲皮素具有很强的抗氧化和抗癌活性。然而，其分子机制尚不清楚。本研究以 JB6 细胞为模型，研究了槲皮素对肿瘤促进作用的影响，该模型已被验证可用于筛选癌症化学预防剂和阐明分子机制。槲皮素可阻断 TPA 诱导的 JB6 P+细胞的癌变转化。用槲皮素预处理 JB6 细胞可下调 UVB 或 TPA 诱导的 AP-1 和 NF-κB 的转录激活。在 AP-1-荧光素酶转基因小鼠的皮肤中，用槲皮素对小鼠进行局部处理可显著阻断 TPA 诱导的 AP-1 转录激活。进一步的研究表明，这些抑制作用可能是通过抑制 MAPKs 磷酸化介导的，包括 ERKs、p38 激酶和 JNKs。此外，槲皮素还可刺激 NF-E2 相关因子（Nrf2）和 GST ARE-荧光素酶活性的激活。彗星试验表明，槲皮素可阻断 UVB 诱导的 DNA 损伤。据我们所知，这些结果首次提供了证据表明，槲皮素通过阻断 MAPK 途径的激活和刺激细胞保护信号，有助于抑制肿瘤转化。此外，据我们所知，这些发现为槲皮素的抗癌作用提供了第一个分子基础。
