Curcumin induces the degradation of cyclin E expression through ubiquitin-dependent pathway and up-regulates cyclin-dependent kinase inhibitors p21 and p27 in multiple human tumor cell lines (Retracted article. See vol. 102, pg. 147, 2016)
Curcumin induces the degradation of cyclin E expression through ubiquitin-dependent pathway and up-regulates cyclin-dependent kinase inhibitors p21 and p27 in multiple human tumor cell lines (Retracted article. See vol. 102, pg. 147, 2016)
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DOI：
10.1016/j.bcp.2006.12.010
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发表时间：
2007-04-01
影响因子：
5.8
通讯作者：
Sethi, Gautam
中科院分区：
文献类型：
--
作者：
Aggarwal, Bharat B.;Banerjee, Sanjeev;Sethi, Gautam
姜黄素是一种众所周知的化学预防剂，已被证明可以抑制多种肿瘤细胞的增殖，其机制尚不完全清楚。Cyclin E是一种在许多人类癌症中过度表达的原癌基因，介导G向S的转化，是姜黄素的潜在靶标。在本报告中，我们证明姜黄素对细胞周期蛋白E表达的剂量和时间依赖性下调与人类前列腺癌和乳腺癌细胞增殖的减少有关。cyclin E表达的抑制不依赖于细胞类型，在雌激素阳性和阴性的乳腺癌细胞、雄激素依赖性和非依赖性的前列腺癌细胞、白血病和淋巴瘤细胞、头颈癌细胞和肺癌细胞中均出现下调。姜黄素诱导的cyclin E下调可被蛋白酶体抑制剂、乳糖蛋白酶和n-乙酰-l -亮氨酸-l -亮氨酸-l -去亮氨酸逆转，提示泛素依赖性蛋白酶体途径的作用。我们发现姜黄素增强了肿瘤细胞周期蛋白依赖性激酶（CDK）抑制剂p21和p27以及肿瘤抑制蛋白p53的表达，但抑制了视网膜母细胞瘤蛋白的表达。姜黄素在细胞周期的G1期也能诱导细胞的聚集。总之，我们的研究结果表明，蛋白酶体介导的细胞周期蛋白E的下调和CDK抑制剂的上调可能有助于姜黄素对各种肿瘤的抗增殖作用。(c) 2006爱思唯尔公司版权所有。
Curcumin, a well-known chemopreventive agent, has been shown to suppress the proliferation of a wide variety of tumor cells through a mechanism that is not fully understood. Cyclin E, a proto-oncogene that is overexpressed in many human cancers, mediates the G, to S transition, is a potential target of curcumin. We demonstrate in this report a dose- and time-dependent down-regulation of expression of cyclin E by curcumin that correlates with the decrease in the proliferation of human prostate and breast cancer cells. The suppression of cyclin E expression was not cell type dependent as down-regulation occurred in estrogen-positive and -negative breast cancer cells, androgen-dependent and -independent prostate cancer cells, leukemia and lymphoma cells, head and neck carcinoma cells, and lung cancer cells. Curcumin-induced down-regulation of cyclin E was reversed by proteasome inhibitors, lactacystin and N-acetyl-L-leuCyl-L-leucyl-L-norleucinal, suggesting the role of ubiquitin-dependent proteasomal pathway. We found that curcumin enhanced the expression of tumor cyclin-dependent kinase (CDK) inhibitofs p21 and p27 as well as tumor suppressor protein p53 but suppressed the expression of retinoblastoma protein. Curcumin also induced the accumulation of the cells in G1 phase of the cell cycle. Overall, our results suggest that proteasome-mediated down-regulation of cyclin E and up-regulation of CDK inhibitors may contribute to the antiproliferative effects of curcumin against various tumors. (c) 2006 Elsevier Inc. All rights reserved.