Department of Physiology, Medical School, Research Institute for Endocrine Sciences, Chonbuk National University, JeonJu 561‑180, Republic of Korea.
Mol Med Rep. 2013 Aug;8(2):557-64. doi: 10.3892/mmr.2013.1551. Epub 2013 Jun 25.
Reactive oxygen species (ROS) influence the signaling of mitogen‑activated protein kinases (MAPKs) involved in cell survival and death. In the present study, the toxicological effect of hydrogen peroxide (H2O2) on HeLa cervical cancer cells was evaluated following treatment with MAPK inhibitors [MAP kinase or ERK kinase (MEK), c‑Jun N‑terminal kinase (JNK) or p38], N‑acetyl cysteine (NAC) and propyl gallate (PG) (well‑known antioxidants), or L‑buthionine sulfoximine [BSO; an inhibitor of glutathione (GSH) synthesis]. Treatment with 100 µM H2O2 inhibited the growth of HeLa cells and induced cell death, which was accompanied by loss of the mitochondrial membrane potential (MMP; ΔΨm). H2O2 did not induce any specific phase arrests of the cell cycle. ROS levels increased, while GSH levels decreased in H2O2‑treated HeLa cells after 1 and 24 h of treatment. The MAPK inhibitors enhanced H2O2‑induced HeLa cell death, while only p38 inhibitor increased ROS levels. Both NAC and PG attenuated H2O2‑induced HeLa cell growth inhibition and death together with the suppression of ROS levels. BSO increased ROS levels in H2O2‑treated HeLa cells without increasing cell death. The levels of MMP (ΔΨm) loss and GSH depletion were not closely associated with the levels of apoptosis in HeLa cells treated with the MAPK inhibitors, NAC, PG or BSO, in the presence of H2O2. In conclusion, H2O2 induced HeLa cell growth inhibition and death. MAPK inhibitors generally enhanced H2O2‑induced HeLa cell death. In particular, p38 inhibitor increased ROS levels in H2O2‑treated HeLa cells, while NAC and PG attenuated H2O2‑induced HeLa cell death by suppressing ROS levels.
活性氧（ROS）影响丝裂原活化蛋白激酶（MAPK）的信号转导，这些激酶参与细胞存活和死亡。在本研究中，使用 MAPK 抑制剂[MAP 激酶或 ERK 激酶（MEK）、c-Jun N-末端激酶（JNK）或 p38]、N-乙酰半胱氨酸（NAC）和没食子酸丙酯（PG）（众所周知的抗氧化剂）或 L-丁硫氨酸亚砜胺[BSO；谷胱甘肽（GSH）合成抑制剂]处理后，评估了过氧化氢（H2O2）对 HeLa 宫颈癌细胞的毒性作用。用 100µM H2O2 处理会抑制 HeLa 细胞的生长并诱导细胞死亡，同时伴随着线粒体膜电位（MMP；ΔΨm）的丧失。H2O2 不会诱导细胞周期的任何特定时相阻滞。在 1 和 24 小时处理后，H2O2 处理的 HeLa 细胞中的 ROS 水平增加，而 GSH 水平下降。MAPK 抑制剂增强了 H2O2 诱导的 HeLa 细胞死亡，而只有 p38 抑制剂增加了 ROS 水平。NAC 和 PG 均减轻了 H2O2 诱导的 HeLa 细胞生长抑制和死亡，同时抑制了 ROS 水平。BSO 在没有增加细胞死亡的情况下增加了 H2O2 处理的 HeLa 细胞中的 ROS 水平。在存在 H2O2 的情况下，MMP（ΔΨm）丧失和 GSH 耗竭的水平与用 MAPK 抑制剂、NAC、PG 或 BSO 处理的 HeLa 细胞中的凋亡水平没有密切关系。总之，H2O2 诱导 HeLa 细胞生长抑制和死亡。MAPK 抑制剂通常增强 H2O2 诱导的 HeLa 细胞死亡。特别是，p38 抑制剂增加了 H2O2 处理的 HeLa 细胞中的 ROS 水平，而 NAC 和 PG 通过抑制 ROS 水平减轻了 H2O2 诱导的 HeLa 细胞死亡。
