Curcumin sensitizes lymphoma cells to DNA damage agents through regulating Rad51-dependent homologous recombination.
Curcumin sensitizes lymphoma cells to DNA damage agents through regulating Rad51-dependent homologous recombination.
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姜黄素通过调节 Rad51 依赖性同源重组使淋巴瘤细胞对 DNA 损伤剂敏感。
DOI：
10.1016/j.biopha.2017.09.078
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Mao Weifeng
中科院分区：
文献类型：
--
作者：
Zhao Qian;Guan Jiawei;Qin Yuanhua;Ren Peng;Zhang Zhiwei;Lv Jian;Sun Shijie;Zhang Cuili;Mao Weifeng
姜黄素是从姜黄（Curcuma longa）根茎中分离得到的天然化合物。它通过阻滞细胞周期和促进细胞凋亡而具有抗肿瘤活性。然而，姜黄素对DNA损伤的影响还没有很好的定义。在这项研究中，我们研究了姜黄素对诱导DNA损伤和对淋巴瘤细胞对抗肿瘤DNA损伤药物的敏感性的影响。Western blot显示姜黄素诱导CH 12 F3淋巴瘤细胞中的γ-H2 AX灶，这表明姜黄素诱导DNA断裂。此外，姜黄素还能降低Rad 51的表达，提示姜黄素通过调节Rad 51依赖的同源重组诱导DNA损伤。Rad 51依赖性同源重组是肿瘤细胞抵抗抗肿瘤DNA损伤药物的重要DNA修复途径，因此我们研究了姜黄素对淋巴瘤细胞对各种化疗药物的增敏作用。我们发现低水平的姜黄素（5 μM）可使淋巴瘤细胞对顺铂、甲磺酸甲酯、羟基脲和喜树碱等抗肿瘤DNA损伤剂敏感。我们还发现姜黄素使CH 12 F3淋巴瘤细胞对DNA-PK和PARP抑制剂敏感。流式细胞仪分析显示姜黄素促进细胞凋亡，蛋白质印迹分析证实姜黄素激活半胱天冬酶3依赖的细胞凋亡。综上所述，这些结果表明，姜黄素通过调节Rad 51依赖的同源重组诱导DNA损伤，并触发caspase 3依赖的凋亡，更重要的是，姜黄素使淋巴瘤细胞对各种DNA损伤药物敏感。因此，姜黄素将是一个有效的代理人的敏感性淋巴瘤细胞的抗肿瘤化疗药物。
Curcumin is a natural compound isolated from the rhizome ofCurcuma longa. It possesses anti-tumor activity through arresting cell cycles and promoting cell apoptosis. However, the effect of curcumin on DNA damage is not well defined. In this study, we investigated the effect of curcumin on inducing DNA damage and on sensitizing lymphoma cells to anti-tumoral DNA damage drugs. Western blot showed curcumin induced γ-H2AX foci in CH12F3 lymphoma cells, which suggests curcumin induces DNA breaks. In addition, curcumin decreased the expression of Rad51, which suggests curcumin induces DNA damage through regulating Rad51-dependant homologous recombination. Rad51-dependant homologous recombination is a vital DNA repair pathway for cancer cells to resist anti-tumoral DNA damage drugs, therefore, we studied the effect of curcumin on the sensitizing lymphoma cells to various chemotherapeutic drugs. We found low level of curcumin (5 μM) sensitized lymphoma cells to anti-tumoral DNA damage agents including cisplatin, methyl methanesulfonate, hydroxyurea and camptothecin. We also found curcumin sensitized CH12F3 lymphoma cells to DNA-PK and PARP inhibitors. Flow cytometry analysis showed curcumin promoted apoptosis and western blot analysis confirmed curcumin activated caspase3-dependent apoptosis. Taken together, these results demonstrate that curcumin induces DNA damage through regulating Rad51-dependant homologous recombination and triggers caspase3-dependent apoptosis, more importantly, curcumin sensitizes lymphoma cells to various DNA damage drugs. Consequently, curcumin would be a potent agent for sensitizing lymphoma cells to anti-tumoral chemotherapeutic agents.
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姜黄素：乳腺癌发生的辛辣调节剂。
DOI：
10.1186/s13046-017-0566-5
发表时间：
2017-07-19
期刊：
Journal of experimental & clinical cancer research : CR
影响因子：
--
作者：
Banik U;Parasuraman S;Adhikary AK;Othman NH
通讯作者：
Othman NH
影响因子：
--
作者：
Bortel N;Armeanu-Ebinger S;Schmid E;Kirchner B;Frank J;Kocher A;Schiborr C;Warmann S;Fuchs J;Ellerkamp V
通讯作者：
Ellerkamp V
MCF-7 和 MDA-MB-231 细胞对姜黄素细胞毒性作用的不同敏感性与 PI3K/Akt-SKP2-Cip/Kips 通路相关
影响因子：
5.8
作者：
Jia T;Zhang L;Duan Y;Zhang M;Wang G;Zhang J;Zhao Z
通讯作者：
Zhao Z
影响因子：
5.3
作者：
Lundin, C;Erixon, K;Helleday, T
通讯作者：
Helleday, T
影响因子：
4.2
作者：
Calaf, Gloria M.;Echiburu-Chau, Carlos;Balajee, Adayabalam S.
通讯作者：
Balajee, Adayabalam S.