Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer
Chemopreventive effect of the non-psychotropic phytocannabinoid cannabidiol on experimental colon cancer
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DOI：
10.1007/s00109-011-0856-x
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发表时间：
2012-08-01
影响因子：
4.7
通讯作者：
Izzo, Angelo A.
中科院分区：
文献类型：
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作者：
Aviello, Gabriella;Romano, Barbara;Izzo, Angelo A.
在西方国家，结肠癌影响着数百万人。大麻二酚是大麻的一种安全和非精神药物成分，发挥药理作用（抗氧化和肠道抗炎）和机制（抑制内源性大麻素酶降解），可能有利于结肠癌的发生。因此，我们在氧化偶氮甲烷（AOM）诱导的小鼠结肠癌模型中研究了其可能的化学预防作用。AOM治疗与异常隐窝病灶（ACF，癌前病变）、息肉和肿瘤形成、磷酸化Akt、iNOS和考克斯-2上调以及caspase-3下调相关。大麻二酚减少ACF，息肉和肿瘤，并抵消AOM诱导的磷酸化Akt和caspase-3的变化。在结直肠癌细胞系中，大麻二酚保护DNA免受氧化损伤，增加内源性大麻素水平，并以CB 1-，TRPV 1-和PPAR γ-拮抗剂敏感的方式减少细胞增殖。结论大麻二酚通过多种机制在体内发挥化学预防作用并减少细胞增殖。
Colon cancer affects millions of individuals in Western countries. Cannabidiol, a safe and non-psychotropic ingredient of Cannabis sativa, exerts pharmacological actions (antioxidant and intestinal antinflammatory) and mechanisms (inhibition of endocannabinoid enzymatic degradation) potentially beneficial for colon carcinogenesis. Thus, we investigated its possible chemopreventive effect in the model of colon cancer induced by azoxymethane (AOM) in mice. AOM treatment was associated with aberrant crypt foci (ACF, preneoplastic lesions), polyps, and tumour formation, up-regulation of phospho-Akt, iNOS and COX-2 and down-regulation of caspase-3. Cannabidiol-reduced ACF, polyps and tumours and counteracted AOM-induced phospho-Akt and caspase-3 changes. In colorectal carcinoma cell lines, cannabidiol protected DNA from oxidative damage, increased endocannabinoid levels and reduced cell proliferation in a CB1-, TRPV1- and PPAR gamma-antagonists sensitive manner. It is concluded that cannabidiol exerts chemopreventive effect in vivo and reduces cell proliferation through multiple mechanisms.