Apoptosis of Human Lung Cancer Cells by Curcumin Mediated through Up-Regulation of "Growth Arrest and DNA Damage Inducible Genes 45 and 153"
Apoptosis of Human Lung Cancer Cells by Curcumin Mediated through Up-Regulation of "Growth Arrest and DNA Damage Inducible Genes 45 and 153"
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DOI：
10.1248/bpb.33.1291
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发表时间：
2010-08-01
影响因子：
2
通讯作者：
Fujiki, Hirota
中科院分区：
文献类型：
--
作者：
Saha, Achinto;Kuzuhara, Takashi;Fujiki, Hirota
“生长停滞和DNA损伤诱导基因45和153”的表达与细胞的凋亡诱导有关。GADD 45是抑癌基因p53的一个效应基因，GADD 153与肿瘤预防的细胞功能相关。姜黄素，从植物姜黄（LINN）中分离出来，已被研究为食品中有前途的癌症预防剂，因为姜黄素，一种酚类和着色化合物，在印度次大陆被广泛摄入。然而，姜黄素的确切作用机制尚未明确阐明。基于我们用绿色茶儿茶素作为癌症预防剂的成功结果，我们研究了GADD 45和153的表达与人肺癌细胞系PC-9的凋亡诱导之间的关系。在我们的研究中，姜黄素以不依赖于p53的方式增加GADD 45和153的表达。姜黄素还能抑制PC-9细胞的生长，诱导细胞周期G（1）/S期阻滞，并诱导细胞凋亡。GADD 45和153小干扰RNA（siRNA）处理抑制姜黄素诱导PC-9细胞凋亡。此外，姜黄素诱导细胞周期蛋白依赖性激酶抑制剂基因p21和p27的表达，而它抑制许多基因的表达，包括Bcl-2，细胞周期蛋白D1，CDK 2，CDK 4和CDK 6。对PC-9细胞的所有结果表明，姜黄素上调GADD 45和153是姜黄素抗癌活性的主要机制。
The expression of "growth arrest and DNA damage inducible genes 45 and 153" is related to apoptotic induction of cells. GADD45 is an effector gene of the tumor suppressor p53, and GADD153 is associated with cellular function of cancer prevention. Curcumin, isolated from the plant Curcuma longa (LINN), has been investigated as a promising cancer preventive in food because curcumin, a phenolic and coloring compound, is widely ingested in the Indian subcontinent. However, the exact mechanisms of action of curcumin have not yet been clearly elucidated. Based on our successful results with green tea catechins as cancer preventive, we studied the relationship between the expression of GADD45 and 153 and apoptotic induction in human lung cancer cell line PC-9. In our study curcumin increased the expression of GADD45 and 153 in a p53-independent manner. Curcumin also inhibited the growth of PC-9 cells and induced G(1)/S arrest of the cell-cycle followed by strong induction of apoptosis. Treatment with GADD45 and 153 small interfering RNAs (siRNAs) inhibited the apoptotic induction in PC-9 cells by curcumin. Moreover, curcumin induced the expression of cyclin dependent kinase inhibitor genes p21 and p27, while it inhibited the expression of numerous genes, including Bcl-2, cyclin D1, CDK2, CDK4 and CDK6. All the results with PC-9 cells suggest that the up-regulation of GADD45 and 153 by curcumin is a prime mechanism in the anticancer activity of curcumin.