Antiproliferative activity and apoptosis-inducing mechanism of constituents from Toona sinensis on human cancer cells.
Antiproliferative activity and apoptosis-inducing mechanism of constituents from Toona sinensis on human cancer cells.
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香椿成分对人癌细胞的抗增殖活性和诱导细胞凋亡机制
DOI：
10.1186/1475-2867-13-12
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发表时间：
2013-02-09
影响因子：
5.8
通讯作者：
Yang S
中科院分区：
文献类型：
--
作者：
Yang S;Zhao Q;Xiang H;Liu M;Zhang Q;Xue W;Song B;Yang S
背景：天然产物，包括植物、微生物和海洋生物，被认为是发现抗癌药物的宝贵资源。方法：本研究从重要的中草药香椿（Toona sinensis）中分离得到具有抗肿瘤活性的化合物。采用MTT法测定了化合物对MGC-803、PC 3、A549、MCF-7和NIH 3 T3细胞的体外抑制活性。通过AO/EB染色、Hoechst 33258染色、原位末端标记、流式细胞术分析和蛋白质印迹分析，探讨活性化合物的抗肿瘤作用机制。结果：从香椿根中分离得到15个化合物。白桦脂酸（Betulonic acid，BTA）和3-氧代-12-烯-28-酸（3-oxours-12-en-28-oic acid，OEA）对MGC-803和PC-3细胞的增殖均有抑制作用，IC_（50）分别为17.7 μM和13.6 μM、26.5 μM和21.9 μM。20 μM和20 μM均可诱导MGC-803细胞凋亡，72 h凋亡率分别为27.3%和24.5%。此外，对肿瘤细胞凋亡信号通路的研究表明，两种化合物均能通过线粒体途径诱导肿瘤细胞凋亡，涉及p53、Bax、caspase 9和caspase 3的表达。此外，BTA和OEA通过诱导癌细胞凋亡表现出有效的抗肿瘤活性。
Background:Natural products, including plants, microorganisms and marines, have been considered as valuable sources for anticancer drug discovery. Many Chinese herbs have been discovered to be potential sources of antitumor drugs.Methods:In the present study, we investigated the antitumor efficacy of the compounds isolated from Toona sinensis, an important herbal medicine. The inhibitory activities of these compounds were investigated on MGC-803, PC3, A549, MCF-7, and NIH3T3 cells in vitro by MTT assay. The mechanism of the antitumor action of active compounds was investigated through AO/EB staining, Hoechst 33258 staining, TUNEL assay, flow cytometry analysis, and western blotting analysis.Results:Fifteen compounds were isolated from the roots of Toona sinensis. Betulonic acid (BTA) and 3-oxours-12-en-28-oic acid (OEA) isolated from the plant inhibited the proliferation of MGC-803 and PC3 cells, with IC50 values of 17.7 μM and 13.6 μM, 26.5 μM and 21.9 μM, respectively. Both could lead to cell apoptosis, and apoptosis ratios reached 27.3% and 24.5% in MGC-803 cells at 72 h after treatment at 20 μM, respectively. Moreover, the study of cancer cell apoptotic signaling pathway indicated that both of them could induce cancer cell apoptosis through the mitochondrial pathway, involving the expressions of p53, Bax, caspase 9 and caspase 3.Conclusions:The study shows that most of the compounds obtained from Toona sinensis could inhibit the growth of human cancer cells. Furthermore, BTA and OEA exhibited potent antitumor activities via induction of cancer cell apoptosis.
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影响因子：
3.7
作者：
Massengale M;Lu B;Pan JJ;Katz JN;Solomon DH
通讯作者：
Solomon DH
DOI：
10.3390/molecules13092114
发表时间：
2008-09-04
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Guo L;Wu JZ;Han T;Cao T;Rahman K;Qin LP
通讯作者：
Qin LP
影响因子：
3.8
作者：
Chintharlapalli S;Papineni S;Lei P;Pathi S;Safe S
通讯作者：
Safe S
影响因子：
2.6
作者：
Cragg, GM;Newman, DJ
通讯作者：
Newman, DJ
影响因子：
2.7
作者：
Kommera, Harish;Kaluderovic, Goran N.;Paschke, Reinhard
通讯作者：
Paschke, Reinhard