Murakami Akira, Takahashi Daisuke, Kinoshita Takashi, Koshimizu Koichi, Kim Ha Won, Yoshihiro Akira, Nakamura Yoshimasa, Jiwajinda Suratwadee, Terao Junji, Ohigashi Hajime
Department of Biotechnological Science, Faculty of Biology-Oriented Science and Technology, Kinki University, Wakayama 649-6493, Japan.
Carcinogenesis. 2002 May;23(5):795-802. doi: 10.1093/carcin/23.5.795.
Zerumbone (ZER), a sesquiterpene from the edible plant Zingiber zerumbet Smith, has recently been found to suppress tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced Epstein-Barr virus activation in a potent manner. In the present study, we evaluated the anti-inflammatory and chemopreventive potentials of ZER in a variety of cell culture experiments. ZER effectively suppressed TPA-induced superoxide anion generation from both NADPH oxidase in dimethylsulfoxide-differentiated HL-60 human acute promyelocytic leukemia cells and xanthine oxidase in AS52 Chinese hamster ovary cells. The combined lipopolysaccharide- and interferon-gamma-stimulated protein expressions of inducible nitric oxide synthase and cyclooxygenase (COX)-2, together with the release of tumor necrosis factor-alpha, in RAW 264.7 mouse macrophages were also markedly diminished. These suppressive events were accompanied with a combined decrease in the medium concentrations of nitrite and prostaglandin E(2), while the expression level of COX-1 was unchanged. ZER inhibited the proliferation of human colonic adenocarcinoma cell lines (LS174T, LS180, COLO205, and COLO320DM) in a dose-dependent manner, while the growth of normal human dermal (2F0-C25) and colon (CCD-18 Co) fibroblasts was less affected. It also induced apoptosis in COLO205 cells, as detected by dysfunction of the mitochondria transmembrane, Annexin V-detected translocation of phosphatidylserine, and chromatin condensation. Intriguingly, alpha-humulene, a structural analog lacking only the carbonyl group in ZER, was virtually inactive in all experiments conducted, indicating that the alpha,beta-unsaturated carbonyl group in ZER may play some pivotal roles in interactions with unidentified target molecule(s). Taken together, our results indicate that ZER is a food phytochemical that has distinct potentials for use in anti-inflammation, chemoprevention, and chemotherapy strategies.
姜酮（ZER）是一种从可食用植物莪术（Zingiber zerumbet Smith）中提取的倍半萜烯，最近发现它能有效抑制肿瘤启动子12 - O - 十四烷酰佛波醇 - 13 - 乙酸酯（TPA）诱导的爱泼斯坦 - 巴尔病毒激活。在本研究中，我们在各种细胞培养实验中评估了ZER的抗炎和化学预防潜力。ZER有效抑制了TPA诱导的超氧阴离子生成，该生成来自二甲基亚砜分化的HL - 60人急性早幼粒细胞白血病细胞中的NADPH氧化酶以及AS52中国仓鼠卵巢细胞中的黄嘌呤氧化酶。在RAW 264.7小鼠巨噬细胞中，脂多糖和干扰素 - γ联合刺激诱导型一氧化氮合酶和环氧化酶（COX）-2的蛋白表达以及肿瘤坏死因子 - α的释放也显著减少。这些抑制作用伴随着培养基中亚硝酸盐和前列腺素E2浓度的联合降低，而COX - 1的表达水平未改变。ZER以剂量依赖的方式抑制人结肠腺癌细胞系（LS174T、LS180、COLO205和COLO320DM）的增殖，而对正常人皮肤（2F0 - C25）和结肠（CCD - 18 Co）成纤维细胞的生长影响较小。它还诱导COLO205细胞凋亡，这通过线粒体跨膜功能障碍、膜联蛋白V检测到的磷脂酰丝氨酸转位以及染色质凝聚得以检测。有趣的是，α - 葎草烯是一种仅在ZER中缺少羰基的结构类似物，在所有进行的实验中几乎没有活性，这表明ZER中的α,β - 不饱和羰基可能在与未确定的靶分子相互作用中发挥一些关键作用。综上所述，我们的结果表明ZER是一种具有独特潜力的食物植物化学物质，可用于抗炎、化学预防和化疗策略。
