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肉碱可减缓 DMH 化学致癌作用小鼠模型结肠癌的发展。

Carnitines slow down tumor development of colon cancer in the DMH-chemical carcinogenesis mouse model.

机构信息

Takis srl, Roma, Italy.

出版信息

J Cell Biochem. 2013 Jul;114(7):1665-73. doi: 10.1002/jcb.24508.

DOI:10.1002/jcb.24508
PMID:23386399
Abstract

Dietary agents are receiving much attention for the chemoprevention of cancer. While curcumin is known to influence several pathways and affect tumor growth in vivo, carnitin and its congeners play a variety of important metabolic functions: are involved in the oxydation of long-chain fatty acids, regulate acyl-CoA levels and influence protein activity and stability by modifying the extent of protein acetylation. In this study we evaluated the efficacy of carnitines in the prevention of cancer development using the 1,2,-dimethylhydrazine (DMH)-induced colon carcinogenesis model. We also assessed whether their combination was able to give rise to increased protection from cancer development. Mice treated with DMH were dosed orally with curcumin and/or carnitine and acylcarnitines for 20 weeks. At the end of the treatment colon samples were collected, and scored for multiple ACF and adenomas. We observed that carnitine and acyl-carnitines had same, if not higher, efficacy than curcumin alone in inhibiting the formation of neoplastic lesions induced by DMH treatment. Interestingly, the combination of curcumin and acetyl-L-carnitine was able to fully inhibit the development of advanced adenoma lesions. Our data unveil the antitumor effects of carnitines and warrant additional studies to further support the adoption of carnitines as cancer chemopreventative agents.

摘要

膳食补充剂在癌症的化学预防方面受到了广泛关注。姜黄素已被证实可以影响多种途径并抑制体内肿瘤生长,而肉碱及其同系物则发挥着多种重要的代谢功能:参与长链脂肪酸的氧化,调节酰基辅酶 A 水平,并通过修饰蛋白质乙酰化程度来影响蛋白质活性和稳定性。在这项研究中,我们使用 1,2-二甲基肼(DMH)诱导的结肠癌发生模型来评估肉碱预防癌症发展的功效。我们还评估了它们的联合使用是否能够带来更高的癌症预防效果。用 DMH 处理的小鼠经口给予姜黄素和/或肉碱和酰基肉碱 20 周。在治疗结束时收集结肠样本,并对多个 ACF 和腺瘤进行评分。我们观察到,肉碱和酰基肉碱在抑制 DMH 处理诱导的肿瘤形成方面的功效与姜黄素单独使用相同(如果没有更高的话)。有趣的是,姜黄素和乙酰-L-肉碱的联合使用能够完全抑制晚期腺瘤病变的发展。我们的数据揭示了肉碱的抗肿瘤作用,并需要进一步的研究来进一步支持将肉碱作为癌症化学预防剂的应用。

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