Transient metals enhance cytotoxicity of curcumin: potential involvement of the NF-kappaB and mTOR signaling pathways.
Transient metals enhance cytotoxicity of curcumin: potential involvement of the NF-kappaB and mTOR signaling pathways.
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发表时间：
2010-09
影响因子：
2
通讯作者：
Jessica R. Lou;Xiaoxi Zhang;Jie Zheng;W. Ding
中科院分区：
文献类型：
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作者：
Jessica R. Lou;Xiaoxi Zhang;Jie Zheng;W. Ding
背景/目的姜黄素是一种金属结合化合物和抗癌剂，但金属参与姜黄素的抗癌作用尚不清楚。本研究探讨了过渡金属在姜黄素诱导的癌细胞毒性中的作用。材料与方法采用细胞活力测定、共聚焦显微镜、Western blot和过氧化氢生成测定等方法检测姜黄素对人肿瘤细胞的金属结合活性和细胞毒性。结果Cu（II）对姜黄素的细胞毒性作用最强。姜黄素和Cu（II）的组合不产生活性氧，维生素E不阻断细胞毒性。姜黄素加Cu（II）提高了细胞内铜水平，并增强了姜黄素诱导的核因子κ B（NF-κB）通路抑制，以及雷帕霉素-raptor（mTOR）信号转导的哺乳动物靶标的改变。结论过渡金属可能通过靶向NF-κB和mTOR信号通路增强姜黄素的细胞毒性。
BACKGROUND/AIM Curcumin has been recognized as a metal-binding compound and an anticancer agent, yet the involvement of metals in the anticancer action of curcumin remains unclear. The present study examined the role of transient metals in curcumin-induced cytotoxicity in cancer cells. MATERIALS AND METHODS Metal-binding activity and cytotoxicity of curcumin were examined in human cancer lines with cell viability assay, confocal microscopy, Western blot, and measurement of hydrogen peroxide generation. RESULTS It was found that Cu (II) most significantly potentiated the cytotoxicity of curcumin among the metals tested. The combination of curcumin and Cu (II) did not generate reactive oxygen species and vitamin E did not block the cytotoxicity. Curcumin plus Cu (II) enhanced intracellular copper levels and potentiated curcumin-induced suppression of the nuclear factor kappa B (NF-κB) pathway, as well as alterations of mammalian target of rapamycin-raptor (mTOR) signaling. CONCLUSION Transient metals enhance the cytotoxicity of curcumin, likely through targeting of the NF-κB and mTOR signaling pathways.