Cycle arrest and apoptosis in MDA-MB-231/Her2 cells induced by curcumin
Cycle arrest and apoptosis in MDA-MB-231/Her2 cells induced by curcumin
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DOI：
10.1016/j.ejphar.2012.05.036
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发表时间：
2012-09-05
影响因子：
5
通讯作者：
Lin, Jen-Kun
中科院分区：
文献类型：
--
作者：
Sun, Shih-Han;Huang, Hsiu-Chen;Lin, Jen-Kun
Her-2或Skp 2过表达的乳腺癌与p27表达减少的乳腺癌重叠。在乳腺癌中，p27的丢失与预后不良有关。姜黄素是姜黄的主要成分，已被发现可稳定乳腺癌中的p27水平，但这种作用是否通过Skp 2或Her 2表达的变化介导仍不清楚。本研究调查姜黄素是否抑制Skp 2介导的p27泛素化在Her 2/Skp 2过表达癌细胞系（MDA-MB-231/Her 2细胞）。结果表明，姜黄素抑制细胞增殖，在较低剂量（30 μ M）下诱导G1期阻滞，在较高剂量（50 μ M）下触发凋亡，并阻断MDA-MB-231/Her 2细胞中的细胞迁移。低剂量姜黄素可显著抑制MDA-MB-231/Her 2细胞的生长，并呈时间和剂量依赖性地增加p27的表达，降低Skp 2、Her 2、Cyclin E、CDK激酶的表达，提示p27、Skp 2和Her 2可能参与了姜黄素对MDA-MB-231/Her 2细胞的生长抑制作用。然而，较高剂量的姜黄素在MDA-MB-231/Her 2细胞中产生剂量依赖性凋亡死亡，这与PARP和半胱天冬酶3的裂解形式有关。研究结果表明，姜黄素对乳腺癌的化学预防具有潜在价值，特别是在Skp 2/Her 2过表达的乳腺癌中。(C)2012 Elsevier B. V.保留所有权利。
Breast cancers with an overexpression of Her-2 or Skp2 overlap with those affected by reduced p27 expression. In breast cancer, the loss of p27 is associated with a poor prognosis. Curcumin, the main constituent of turmeric, has been found to stabilize p27 levels in breast cancer, but whether this effect is mediated through changes in Skp2 or Her2 expression remains unclear. This study investigates whether curcumin inhibits Skp2-mediated p27 ubiquitination in Her2/Skp2-overexpressing cancer cell lines (MDA-MB-231/Her2 cells). The results show that curcumin represses cell proliferation, induces G1 arrest at a lower dosage (30 mu M), triggers apoptosis at a higher dosage (50 mu M) and blocks cell migration in MDA-MB-231/Her2 cells. A low dose of curcumin increases p27 and decreases Skp2, Her2, Cyclin E, CDK kinases in a time- and dose-dependent manner, suggesting that p27, Skp2 and Her2 may be involved in the growth inhibition in MDA-MB-231/Her2 cells induced by curcumin. However, higher doses of curcumin produce a dose-dependent apoptotic death in MDA-MB-231/Her2 cells, which is related to cleaved forms of PARP and caspase 3. The findings indicate that curcumin is of potential value for the chemoprevention of breast cancer, especially in breast cancer with Skp2/Her2 overexpression. (C) 2012 Elsevier B.V. All rights reserved.