PNAS:阿司匹林和白藜芦醇通过杀死四倍体细胞来预防癌症

2014年2月13日 讯 --法国Gustave Roussy研究所的Guido Kroemer博士领导的研究团队发现阿司匹林和白藜芦醇能够杀死小鼠和人中的四倍体细胞，阿司匹林和白藜芦醇能够通过清除异常细胞来预防癌症的发生。相关报道发表在近期的PNAS杂志上。

四倍体细胞中每条染色体有四个拷贝，而不是通常的两个拷贝。四倍体细胞一般在形成时就会死亡。及时没有死亡也会被机体免疫系统识别并清除。但是肿瘤发生早期会出现大量的四倍体细胞。科学家在支气管癌，食管癌，胃癌，乳腺癌，结肠癌，子宫癌和前列腺癌等多种癌症早期都发现有四倍体细胞的异常聚集。有研究称癌前细胞的抑癌因子失活也会导致四倍体细胞形成。

虽然科学家知道破坏四倍体细胞能够预防癌症，但是到现在科学家还没有很好的杀死四倍体细胞但是不影响正常细胞的方法。DNA破坏因子并不能杀死四倍体细胞。细胞分裂相关酶的抑制剂能够破坏四倍体细胞，但是同时也影响正常细胞的分裂。

阿司匹林和白藜芦醇都具有预防癌症的功能，Kroemer博士想知道它们是否是通过破坏四倍体细胞来预防癌症的。科学家构建了易患肠道癌的转基因小鼠，发现该小鼠比正常小鼠具有更多的四倍体细胞。科学家给该转基因小鼠服用阿司匹林和白藜芦醇，发现该小鼠的四倍体细胞数量减少了，同时小鼠发展为癌症的概率也降低了。

科学家在培养细胞体系进一步验证了该结果，发现白藜芦醇能够杀死四倍体细胞，并不影响正常二倍体细胞的生存。但是其他细胞毒性物质，如顺铂，槲皮黄酮和百草枯等杀死二倍体细胞的数量比四倍体细胞多。

阿司匹林和白藜芦醇都能激活AMPK通路，Kroemer博士认为两者激活的AMPK通路的过表达是杀死四倍体细胞的原因。于是科学家激活二倍体和四倍体细胞内AMPK通路，发现只有四倍体细胞死亡。科学家认为这可能是因为四倍体细胞比二倍体细胞对AMPK的耐受能力低。



Resveratrol and aspirin eliminate tetraploid cells for anticancer chemoprevention

Delphine Lissa, Laura Senovilla, Santiago Rello-Varona, Ilio Vitale, Micka?l Michaud, Federico Pietrocola, Alice Boilève, Florine Obrist, Chloé Bordenave, Pauline Garcia, Judith Michels, Mohamed Jemaà, Oliver Kepp, Maria Castedo, and Guido Kroemer

Tetraploidy constitutes a genomically metastable state that can lead to aneuploidy and genomic instability. Tetraploid cells are frequently found in preneoplastic lesions, including intestinal cancers arising due to the inactivation of the tumor suppressor adenomatous polyposis coli (APC). Using a phenotypic screen, we identified resveratrol as an agent that selectively reduces the fitness of tetraploid cells by slowing down their cell cycle progression and by stimulating the intrinsic pathway of apoptosis. Selective killing of tetraploid cells was observed for a series of additional agents that indirectly or directly stimulate AMP-activated protein kinase (AMPK) including salicylate, whose chemopreventive action has been established by epidemiological studies and clinical trials. Both resveratrol and salicylate reduced the formation of tetraploid or higher-order polyploid cells resulting from the culture of human colon carcinoma cell lines or primary mouse epithelial cells lacking tumor protein p53 (TP53, best known as p53) in the presence of antimitotic agents, as determined by cytofluorometric and videomicroscopic assays. Moreover, oral treatment with either resveratrol or aspirin, the prodrug of salicylate, repressed the accumulation of tetraploid intestinal epithelial cells in the ApcMin/+ mouse model of colon cancer. Collectively, our results suggest that the chemopreventive action of resveratrol and aspirin involves the elimination of tetraploid cancer cell precursors.

預防腸癌也有作用

这里有篇文章是谈白藜芦醇的，还有有关白藜芦醇的保健品

http://www.guokr.com/article/440031/

学习了，白藜芦醇在葡萄、花生、蓝莓等很多植物性食物中都存在。