Differential inhibition of protein translation machinery by curcumin in normal, immortalized, and malignant oral epithelial cells.
Differential inhibition of protein translation machinery by curcumin in normal, immortalized, and malignant oral epithelial cells.
复制标题
DOI：
10.1158/1940-6207.capr-09-0076
复制
发表时间：
2010-03
期刊：
影响因子：
--
通讯作者：
Lotan R
中科院分区：
文献类型：
--
作者：
Chakravarti N;Kadara H;Yoon DJ;Shay JW;Myers JN;Lotan D;Sonenberg N;Lotan R
姜黄素在预防口腔癌发生方面显示出一些前景，其机制尚未完全解决。信使RNA翻译在真核生物中由eIF 4F复合物介导，该复合物由真核生物翻译起始因子eIF 4 E、eIF 4G和eIF 4A组成。这些组分中的一些的过度表达或起始阻遏蛋白（4 E-BP 1）的失活已经通过影响细胞存活、血管生成和肿瘤生长和侵袭而与癌症发展包括口腔癌发生有关。在这项研究中，我们研究了姜黄素在正常、永生化正常、白斑和恶性细胞中不同地影响翻译机制的可能性。姜黄素处理在体外抑制永生化的口腔粘膜上皮细胞（NOM 9-CT）和白斑细胞（MSK-Leuk 1 s），以及在UMSCC 22 B和SCC 4细胞来源于头颈部鳞状细胞癌的生长。姜黄素仅对正常口腔上皮细胞（NOM 9）的生长产生轻微影响。在永生化、白斑和癌细胞中，姜黄素通过抑制4 E-BP 1、eIF 4G、eIF 4 B和Mnk 1的磷酸化来抑制帽依赖性翻译，并且还降低eIF 4 E和Mnk 1的总水平。我们的研究结果表明，永生化的正常、白斑和恶性口腔细胞对姜黄素更敏感，并且比正常口腔细胞显示出更大的蛋白质翻译机制调节，这表明靶向该过程可能是一般化学预防的重要方法，特别是对于姜黄素。
Curcumin has shown some promise in prevention of oral carcinogenesis by mechanism(s) that are still not completely resolved. Messenger-RNA translation is mediated in eukaryotes by the eIF4F complex comprised of eukaryotic translation initiation factors eIF4E, eIF4G, and eIF4A. Over expression of some of these components or inactivation of initiation repressor proteins (4E-BP1) has been implicated in cancer development including oral carcinogenesis by affecting cell survival, angiogenesis, and tumor growth and invasion. In this study, we examined the possibility that curcumin affects the translational machinery differently in normal, immortalized normal, leukoplakia and malignant cells. Curcumin treatment in vitro inhibited the growth of immortalized oral mucosa epithelial cells (NOM9-CT) and the leukoplakia cells (MSK-Leuk1s) as well as in the UMSCC22B and SCC4 cells derived from head and neck squamous cell carcinoma. Curcumin only exerted minor effects on the growth of normal oral epithelial cells (NOM9). In the immortalized, leukoplakia and cancer cells, curcumin inhibited cap-dependent translation by suppressing the phosphorylation of 4E-BP1, eIF4G, eIF4B and Mnk1, and also reduced the total levels of eIF4E and Mnk1. Our findings demonstrate that immortalized normal, leukoplakia and malignant oral cells are more sensitive to curcumin and show greater modulation of protein translation machinery than the normal oral cells indicating that targeting this process may be an important approach to chemoprevention in general and for curcumin in particular.