Osthole attenuates doxorubicin-induced apoptosis in PC12 cells through inhibition of mitochondrial dysfunction and ROS production.

Osthole attenuates doxorubicin-induced apoptosis in PC12 cells through inhibition of mitochondrial dysfunction and ROS production.
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DOI:
10.1155/2014/156848
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发表时间:
2014
影响因子:
--
通讯作者:
Mohammadi-Motlagh HR
Mohammadi-Motlagh HR
中科院分区:
生物学3区
文献类型:
--
作者:
Shokoohinia Y;Hosseinzadeh L;Moieni-Arya M;Mostafaie A;Mohammadi-Motlagh HR

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多柔比星(DOX)是一种有效的广谱化疗药物,用于治疗多种类型的癌症。尽管其有效性,但它具有广泛的毒副作用,其中许多很可能是由其固有的促氧化活性引起的。据报道,DOX对正常组织,包括脑组织具有毒性作用。本实验研究了从白菱叶Prangos ferulacea(L.)Lindl.对DOX诱导的PC 12神经元模型细胞氧化应激和凋亡的影响。用不同浓度的DOX处理PC 12细胞2 h后,用蛇床子素预处理。24 h后检测细胞存活率、线粒体膜电位(MMP)、caspase-3活性、Bax/Bcl-2表达比值及细胞内ROS产生情况。结果表明,蛇床子素预处理可显著降低DOX诱导的PC 12细胞活力下降、caspase-3活性、Bax/Bcl-2比值升高和细胞内ROS的产生。蛇床子素预处理可使PC 12细胞MMP表达增加。总之,我们的研究结果表明,用无毒浓度的蛇床子素预处理保护PC 12细胞从DOX介导的凋亡通过抑制ROS的产生。
Doxorubicin (DOX) is a potent, broad-spectrum chemotherapeutic drug used for treatment of several types of cancers. Despite its effectiveness, it has a wide range of toxic side effects, many of which most likely result from its inherent prooxidant activity. It has been reported that DOX has toxic effects on normal tissues, including brain tissue. In the current study, we investigated the protective effect of osthole isolated from Prangos ferulacea (L.) Lindl. on oxidative stress and apoptosis induced by DOX in PC12 as a neuronal model cell line. PC12 cells were pretreated with osthole 2 h after treatment with different concentrations of DOX. 24 h later, the cell viability, mitochondrial membrane potential (MMP), the activity of caspase-3, the expression ratio of Bax/Bcl-2, and the generation of intracellular ROS were detected. We found that pretreatment with osthole on PC12 cells significantly reduced the loss of cell viability, the activity of caspase-3, the increase in Bax/Bcl-2 ratio, and the generation of intracellular ROS induced by DOX. Moreover, pretreatment with osthole led to an increase in MMP in PC12 cells. In conclusion, our results indicated that pretreatment with nontoxic concentrations of osthole protected PC12 cells from DOX-mediated apoptosis by inhibition of ROS production.
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