Basic research for development of cancer prevention by inhibitory effect of food constituents on the signal transduction pathways associated with carcinogenesis

MEK-ERK或PI3K-Akt信号转导通路在许多肿瘤中被加速，被认为不仅是癌症治疗的重要分子靶点，也是癌症预防的重要分子靶点。为了针对食物成分致癌的主要信号转导通路，开发一种新的癌症预防策略，研究了油菜素或脱氢姜黄酮对人结肠癌细胞的生长抑制作用，并对其分子机制进行了分析。从卷心菜或西兰花等十字花科蔬菜中提取的油菜素通过抑制PI3K-Akt途径抑制了人结肠癌HT-29细胞的生长。脱氢姜黄酮来源于生姜，是姜黄素的半结构类似物，可抑制MEK-ERK通路。脱氢姜黄酮抑制了HT-29细胞的生长，并与细胞内活性氧的积累有关。此外，PI3K抑制剂和组蛋白脱乙酰酶抑制剂联合应用对人子宫内膜癌HEC-1A细胞的生长也有一定的抑制作用。

MEK-ERK or PI3K-Akt signal transduction pathways are accelerated in many cancers and considered to be the very important molecular targets not only for the cancer therapy but also for the cancer prevention. To develop a novel strategy for cancer prevention targeting the major signal transduction pathways associated with carcinogenesis by food constituents, growth inhibitory effect of brassinin ordehydrozingerone on human colon cancer cells was studied and the molecular mechanisms were analyzed. Brassinin, derived from cruciferous vegetables like cabbage or broccoli, repressed the growth of human colon cancer HT -29 cells mediated by inhibition of PI3K-Akt pathway . Dehydrozingerone, derived from a ginger, and is known as a structural half analogue of curcumin, which is known to inhibit MEK-ERK pathway. Dehydrozingerone repressed the growth of HT -29 cells in association with accumulation of intracellular reactive oxygen species (ROS). In addition, combination of a PI3K inhibitor with histone deacetylase inhibitor was shown to be useful for growth inhibition of human endometrial carcinoma HEC-1A cells.