Isoliquiritigenin Enhances Radiosensitivity of HepG2 Cells via Disturbance of Redox Status
Isoliquiritigenin Enhances Radiosensitivity of HepG2 Cells via Disturbance of Redox Status
复制标题
异甘草素通过干扰氧化还原状态增强 HepG2 细胞的放射敏感性
DOI：
10.1007/s12013-012-9447-x
复制
发表时间：
2013-04-01
影响因子：
2.6
通讯作者：
Wang, Zhen-hua
中科院分区：
文献类型：
--
作者：
Sun, Chao;Zhang, Hong;Wang, Zhen-hua
氧化还原平衡在维持细胞生长和存活中起着重要作用。这种平衡的破坏会改变正常的细胞过程。癌细胞中经常发现过量的活性氧(ROS)。然而，癌细胞有一个有效的抗氧化系统来抵消增加的ROS生成。这种高抗氧化能力也有利于抵抗药物和辐射。在这里，我们发现，异甘草素(ISL)，一种天然抗氧化剂，在处理0.5、1和2小时后以时间依赖的方式有效地降低HepG2细胞中的ROS。ROS的降低导致氧化还原失衡和还原应激。为了适应这种状态，调节抗氧化酶系统的核因子红系相关因子2显著降低。抗氧化酶在ISL处理后6h达到最低水平。在ISL处理6h后，仍有内源性ROS产生，ROS明显高于ISL处理前，导致细胞氧化还原失衡，从还原应激转变为氧化应激。在这一阶段，对细胞进行X射线照射。过量的ROS诱导严重的氧化应激，导致放射增敏。因此，我们得出结论，ISL通过破坏细胞的氧化还原状态，最终增强细胞对放射的敏感性，从而诱导氧化应激。
Redox balance plays an important role in the maintenance of cell growth and survival. Disturbance of this equilibrium can alter normal cellular processes. Excessive reactive oxygen species (ROS) are often found in cancer cells. However, cancer cells have an efficient antioxidant system to counteract the increased generation of ROS. This high antioxidant capacity also favors resistance to drugs and radiation. Here, we show that isoliquiritigenin (ISL), a natural antioxidant, effectively decreased ROS in HepG2 cells in a time-dependant manner at 0.5, 1, and 2 h of treatment. The decreased ROS caused redox imbalance and reductive stress. To adapt to this state, nuclear factor erythroid-2-related factor 2, which regulates the antioxidant enzyme system, was significantly decreased. Antioxidant enzymes reached their lowest level at 6 h after ISL treatment. Endogenous ROS were still being generated so after 6 h of ISL treatment, ROS were clearly higher than before ISL treatment, causing redox imbalance in the HepG2 cells which changed from reductive to oxidative stress. At this stage, cells were irradiated with X-rays. The excess ROS induced serious oxidative stress, resulting in radiosensitization. Therefore, we concluded that ISL induced oxidative stress by disturbing the redox status and ultimately enhancing the radiosensitivity of HepG2 cells.