Chuang S E, Kuo M L, Hsu C H, Chen C R, Lin J K, Lai G M, Hsieh C Y, Cheng A L
Division of Cancer Research, National Health Research Institutes, Taipei, Taiwan.
Carcinogenesis. 2000 Feb;21(2):331-5. doi: 10.1093/carcin/21.2.331.
Curcumin has been widely used as a spice and coloring agent in foods. Recently, curcumin was found to possess chemopreventive effects against skin cancer, forestomach cancer, colon cancer and oral cancer in mice. Clinical trials of curcumin for prevention of human cancers are currently ongoing. In this study, we examine the chemopreventive effect of curcumin on murine hepatocarcinogenesis. C3H/HeN mice were injected i.p. with N-diethylnitrosamine (DEN) at the age of 5 weeks. The curcumin group started eating 0.2% curcumin-containing diet 4 days before DEN injection until death. The mice were then serially killed at the scheduled times to examine the development of hepatocellular carcinoma (HCC) and changes in intermediate biological markers. At the age of 42 weeks, the curcumin group, as compared with the control group (DEN alone), had an 81% reduction in multiplicity (0.5 versus 2.57) and a 62% reduction in incidence (38 versus 100%) of development of HCC. A series of intermediate biological markers were examined by western blot. While hepatic tissues obtained from the DEN-treated mice showed a remarkable increase in the levels of p21(ras), PCNA and CDC2 proteins, eating a curcumin-containing diet reversed the levels to normal values. These results indicate that curcumin effectively inhibits DEN-induced hepatocarcinogenesis in the mouse. The underlying mechanisms of the phenomenon and the feasibility of using curcumin in the chemoprevention of human HCC should be further explored.
姜黄素已被广泛用作食品中的香料和着色剂。最近，人们发现姜黄素对小鼠的皮肤癌、前胃癌、结肠癌和口腔癌具有化学预防作用。目前正在进行姜黄素预防人类癌症的临床试验。在本研究中，我们检测了姜黄素对小鼠肝癌发生的化学预防作用。5周龄的C3H/HeN小鼠腹腔注射N-二乙基亚硝胺（DEN）。姜黄素组在注射DEN前4天开始食用含0.2%姜黄素的饮食直至死亡。然后在预定时间对小鼠进行连续处死，以检测肝细胞癌（HCC）的发生情况以及中间生物学标志物的变化。在42周龄时，与对照组（仅注射DEN）相比，姜黄素组HCC发生的瘤数减少了81%（0.5对2.57），发病率降低了62%（38%对100%）。通过蛋白质印迹法检测了一系列中间生物学标志物。从经DEN处理的小鼠获得的肝组织中，p21(ras)、PCNA和CDC2蛋白水平显著升高，而食用含姜黄素的饮食可使这些水平恢复到正常。这些结果表明，姜黄素可有效抑制DEN诱导的小鼠肝癌发生。该现象的潜在机制以及姜黄素用于人类HCC化学预防的可行性有待进一步探索。
