Combined xanthorrhizol-curcumin exhibits synergistic growth inhibitory activity via apoptosis induction in human breast cancer cells MDA-MB-231.
Combined xanthorrhizol-curcumin exhibits synergistic growth inhibitory activity via apoptosis induction in human breast cancer cells MDA-MB-231.
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DOI：
10.1186/1475-2867-9-1
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发表时间：
2009-01-02
影响因子：
5.8
通讯作者：
Ismail, Zakiah
中科院分区：
文献类型：
--
作者：
Cheah, Yew Hoong;Nordin, Fariza Juliana;Sarip, Rozie;Tee, Thiam Tsui;Azimahtol, Hawariah Lope Pihie;Sirat, Hasnah M.;Abd Rashid, Badrul Amini;Abdullah, Noor Rain;Ismail, Zakiah
有研究表明，天然产物的联合作用可提高抗癌效果。本研究旨在探讨黄菌素与姜黄素联用对人乳腺癌MDA-MB-231细胞通过诱导凋亡产生协同抑制生长作用的可能性。根据硫代丹B （sulforhodamine B， SRB）法生成的黄菌素与姜黄素固定组合的对数剂量-反应曲线，计算产生50%生长抑制的有效剂量（GI50）。采用实验GI50值，通过等密度分析和联合指数法确定联合处理的增效活性。本研究进一步探讨了联合治疗诱导细胞死亡的方式。等孔分析表明，黄菌根醇和姜黄素同时加入培养物时，两种物质的相互作用是协同的，而依次加入培养物时，两种物质的相互作用只是相加的。然后将协同联合处理应用于培养物，研究该处理诱导的细胞死亡模式。使用抗体mitoccapture™的免疫荧光染色显示线粒体跨膜电位改变的可能性，这是细胞凋亡的标志之一。Hoechst 33258核染色法显示MDA-MB-231细胞凋亡率随药物作用而升高。DNA片段分析进一步证实凋亡细胞死亡，黄菌根-姜黄素处理诱导核小体间DNA切除。这是黄菌素和姜黄素首次联合作用于MDA-MB-231细胞，我们的研究结果为黄菌素联合作用于MDA-MB-231细胞通过诱导细胞凋亡而协同抑制细胞生长的假说提供了实验支持。
It has been suggested that combined effect of natural products may improve the treatment effectiveness in combating proliferation of cancer cells. The present study was undertaken to evaluate the possibility that the combination of xanthorrhizol and curcumin might show synergistic growth inhibitory effect towards MDA-MB-231 human breast cancer cells via apoptosis induction. The effective dose that produced 50% growth inhibition (GI50) was calculated from the log dose-response curve of fixed-combinations of xanthorrhizol and curcumin generated from the sulforhodamine B (SRB) assay. The experimental GI50 value was used to determine the synergistic activity of the combination treatment by isobolographic analysis and combination-index method. Further investigation of mode of cell death induced by the combination treatment was conducted in the present study. Isobole analysis revealed that substances interaction was synergistic when xanthorrhizol and curcumin were added concurrently to the cultures but merely additive when they were added sequentially. The synergistic combination treatment was then applied to the cultures to investigate the mode of cell death induced by the treatment. Immunofluorescence staining using antibody MitoCapture™ revealed the possibility of altered mitochondrial transmembrane potential, which is one of the hallmark of apoptosis. Hoechst 33258 nuclear staining assay showed the rate of apoptosis of MDA-MB-231 cells to increase in response to the treatment. Apoptotic cell death was further confirmed by DNA fragmentation assay, where internucleosomal excision of DNA was induced upon treatment with xanthorrhizol-curcumin. This is the first time the combined cytotoxic effect of xanthorrhizol and curcumin on MDA-MB-231 cells has been documented and our findings provide experimental support to the hypothesis that combined xanthorrhizol-curcumin showed synergistic growth inhibitory activity on MDA-MB-231 cells via apoptosis induction.
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影响因子：
3.4
作者：
Hung, Wei-Chin;Chen, Fang-Yu;Huang, Huey W.
通讯作者：
Huang, Huey W.
影响因子：
5.8
作者：
Hong, C;Firestone, GL;Bjeldanes, LF
通讯作者：
Bjeldanes, LF
影响因子：
2.2
作者：
Bartsch, JE;Staren, ED;Appert, HE
通讯作者：
Appert, HE
DOI：
10.1016/j.bbrc.2004.11.020
发表时间：
2005-01-07
影响因子：
3.1
作者：
Choi, MA;Kim, SH;Park, KK
通讯作者：
Park, KK
影响因子：
4.7
作者：
Chung, Won Yoon;Park, Jae Hee;Park, Kwang Kyun
通讯作者：
Park, Kwang Kyun