Ding Min, Feng Rentian, Wang Shiow Y, Bowman Linda, Lu Yongju, Qian Yong, Castranova Vincent, Jiang Bing-Hua, Shi Xianglin
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505.
Pathology and Physiology Research Branch, Health Effects Laboratory Division, National Institute for Occupational Safety and Health, Morgantown, West Virginia 26505.
J Biol Chem. 2006 Jun 23;281(25):17359-17368. doi: 10.1074/jbc.M600861200. Epub 2006 Apr 17.
Epidemiological data suggest that consumption of fruits and vegetables has been associated with a lower incidence of cancer. Cyanidin-3-glucoside (C3G), a compound found in blackberry and other food products, was shown to possess chemopreventive and chemotherapeutic activity in the present study. In cultured JB6 cells, C3G was able to scavenge ultraviolet B-induced OH and O2- radicals. In vivo studies indicated that C3G treatment decreased the number of non-malignant and malignant skin tumors per mouse induced by 12-O-tetradecanolyphorbol-13-acetate (TPA) in 7,12-dimethylbenz[a]anthracene-initiated mouse skin. Pretreatment of JB6 cells with C3G inhibited UVB- and TPA-induced transactivation of NF-kappaB and AP-1 and expression of cyclooxygenase-2 and tumor necrosis factor-alpha. These inhibitory effects appear to be mediated through the inhibition of MAPK activity. C3G also blocked TPA-induced neoplastic transformation in JB6 cells. In addition, C3G inhibited proliferation of a human lung carcinoma cell line, A549. Animal studies showed that C3G reduced the size of A549 tumor xenograft growth and significantly inhibited metastasis in nude mice. Mechanistic studies indicated that C3G inhibited migration and invasion of A549 tumor cells. These finding demonstrate for the first time that a purified compound of anthocyanin inhibits tumor promoter-induced carcinogenesis and tumor metastasis in vivo.
流行病学数据表明，食用水果和蔬菜与较低的癌症发病率相关。花青素-3-葡萄糖苷（C3G）是一种在黑莓和其他食品中发现的化合物，在本研究中显示具有化学预防和化学治疗活性。在培养的JB6细胞中，C3G能够清除紫外线B诱导的*OH和O2-*自由基。体内研究表明，C3G处理可减少7,12-二甲基苯并[a]蒽引发的小鼠皮肤中由12-O-十四烷酰佛波醇-13-乙酸酯（TPA）诱导的每只小鼠非恶性和恶性皮肤肿瘤的数量。用C3G预处理JB6细胞可抑制UVB和TPA诱导的NF-κB和AP-1的反式激活以及环氧合酶-2和肿瘤坏死因子-α的表达。这些抑制作用似乎是通过抑制MAPK活性介导的。C3G还可阻断TPA诱导的JB6细胞的肿瘤转化。此外，C3G可抑制人肺癌细胞系A549的增殖。动物研究表明，C3G可减小A549肿瘤异种移植瘤的大小，并显著抑制裸鼠中的转移。机制研究表明，C3G可抑制A549肿瘤细胞的迁移和侵袭。这些发现首次证明，一种纯化的花青素化合物在体内可抑制肿瘤启动子诱导的致癌作用和肿瘤转移。
