Gambogic acid promotes apoptosis and resistance to metastatic potential in MDA-MB-231 human breast carcinoma cells
Gambogic acid promotes apoptosis and resistance to metastatic potential in MDA-MB-231 human breast carcinoma cells
复制标题
藤黄酸促进 MDA-MB-231 人乳腺癌细胞的凋亡和抗转移能力。
DOI：
10.1139/o2012-030
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发表时间：
2012-12-01
影响因子：
2.9
通讯作者：
Guo, Qinglong
中科院分区：
文献类型：
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作者：
Li, Chenglin;Qi, Qi;Guo, Qinglong
藤黄酸（GA）是一种有效的抗肿瘤药物，在体外和体内对癌细胞具有多种作用。低浓度GA（0.3-1.2 μmol/L）可抑制人乳腺癌细胞的侵袭而不影响细胞活力。为了获得对乳腺癌的抑制的整体概况，采用较高浓度的GA和自发转移动物模型。GA（3和6 μmol/L）诱导MDA-MB-231细胞凋亡和活性氧（ROS）的积累。此外，GA诱导PARP裂解，caspase-3，caspase-8和caspase-9的活化，以及Bax/Bcl-2的比例增加。此外，还观察到凋亡诱导因子（AIF）的移位和线粒体细胞色素c（Cyt c）的释放，表明GA通过ROS积累和线粒体凋亡途径诱导细胞凋亡。GA还通过阻断Akt/mTOR信号传导抑制细胞存活。GA对裸鼠移植瘤的生长和肺转移有明显的抑制作用。总的来说，这些数据进一步支持GA对人乳腺癌细胞的多种作用，以及其抑制肿瘤生长和预防人类癌症转移的潜在应用。
Gambogic acid (GA) is considered a potent anti-tumor agent for its multiple effects on cancer cells in vitro and in vivo. Low concentrations of GA (0.3–1.2 µmol/L) can suppress invasion of human breast carcinoma cells without affecting cell viability. To get a whole profile of the inhibition on breast cancers, higher concentrations of GA and spontaneous metastatic animal models were employed. Treatment with GA (3 and 6 µmol/L) induced apoptosis in MDA-MB-231 cells and the accumulation of reactive oxygen species (ROS). Furthermore, GA induced PARP cleavage, activation of caspase-3, caspase-8, and caspase-9, as well as an increased ratio of Bax/Bcl-2. Moreover, the translocation of apoptotic inducing factor (AIF) and the release of cytochrome c (Cyt c) from mitochondria were observed, indicating that GA induced apoptosis through accumulation of ROS and mitochondrial apoptotic pathway. GA also inhibited cell survival via blocking Akt/mTOR signaling. In vivo, GA significantly inhibited the xenograft tumor growth and lung metastases in athymic BALB/c nude mice bearing MDA-MB-231 cells. Collectively, these data provide further support for the multiple effects of GA on human breast cancer cells, as well as for its potential application to inhibit tumor growth and prevent metastasis in human cancers.