Institute of Endocrinology and Experimental Oncology, IEOS CNR, Via Pansini 5, 80131 Naples, Italy.
Eur J Cancer. 2012 Nov;48(16):3112-22. doi: 10.1016/j.ejca.2012.02.062. Epub 2012 Mar 14.
We previously showed that methyl-F-anandamide, a stable analogue of the anandamide, inhibited the growth and the progression of cultured human breast cancer cells. As accumulating evidences indicate that the constitutive activation of the canonical Wnt pathway in human breast cancer may highlight a key role for aberrant activation of the β-catenin-TCF cascade and tumour progression, we studied the anandamide effect on the key elements of Wnt pathway in breast cancer cells. In this study we described that the treatment of human breast cancer cells, MDA MB 231 cells, with methyl-F-anandamide reduced protein levels of β-catenin in the cytoplasmic and nuclear fractions inhibiting the transcriptional activation of T Cell Factor (TCF) responsive element (marker for β-catenin signalling). The anandamide treatment resulted in up-regulation of epithelial markers, like E-cadherin with a concomitant decrease in protein levels of mesenchymal markers, including vimentin and Snail1. We, furthermore, observed that the induction of experimental epithelial-mesenchymal transition by exposure to adriamycin in MCF7 human breast cancer cell line was inhibited by anandamide treatment. In the present study we reported a novel anticancer effect of anandamide involving the inhibition of epithelial-mesenchymal transition, a process triggered during progression of cancer to invasive state.
我们之前曾表明，甲基-F-花生四烯酰胺，一种大麻素的稳定类似物，能够抑制培养的人乳腺癌细胞的生长和进展。由于越来越多的证据表明，人乳腺癌中组成型激活经典 Wnt 途径可能突出了β-连环蛋白-TCF 级联的异常激活和肿瘤进展的关键作用，我们研究了大麻素对乳腺癌细胞中 Wnt 途径关键元素的影响。在这项研究中，我们描述了用甲基-F-花生四烯酰胺处理人乳腺癌细胞 MDA MB 231 细胞，降低了细胞质和核部分中β-连环蛋白的蛋白水平，抑制了 T 细胞因子（TCF）反应元件的转录激活（β-连环蛋白信号的标志物）。大麻素处理导致上皮标志物，如 E-钙黏蛋白的表达上调，同时间充质标志物，包括波形蛋白和 Snail1 的蛋白水平下降。此外，我们观察到，用阿霉素处理 MCF7 人乳腺癌细胞系诱导实验性上皮-间充质转化被大麻素处理所抑制。在本研究中，我们报道了大麻素的一种新的抗癌作用，涉及上皮-间充质转化的抑制，这是癌症进展到侵袭状态时触发的一个过程。
