The effect of MAPK inhibitors and ROS modulators on cell growth and death of H2O2-treated HeLa cells

Abstract

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.

Danshensu Inhibits β-Adrenergic Receptors-Mediated Cardiac Fibrosis by ROS/p38 MAPK Axis

“…[38][39][40][41] However, some studies demonstrated contrary views. [42][43][44] The different regulation networks may cause varied biological effects in diverse cells and organisms. To elucidate the specific relationship between ROS and p38, we checked the effect of NAC and SB202190, selective inhibitors of ROS and p38, respectively.…”

An Acetamide Derivative as a Camptothecin Sensitizer for Human Non‐Small‐Cell Lung Cancer Cells through Increased Oxidative Stress and JNK Activation

“…The mitogen-activated protein kinases (MAPK) family is considered to be one of the major ROS-induced signal pathways and is involved in cellular survival, proliferation, and cell death [55]. Among the members of the MAPK family, c-Jun N-terminal protein kinase (JNK) is believed to regulate proapoptotic pathways and lead to cell death [56].…”

CB2 Receptor Activation Ameliorates the Proinflammatory Activity in Acute Lung Injury Induced by Paraquat

“…Sustained ROS generation activated MAPKs (e.g., p38MAPK, ERK1/2, and JNK1/2) [41, 42] and proinflammatory pathways (e.g., NF- κ B) [43, 44] in various cell types, in turn remodulating/regulating important inflammatory and cell survival and death processes in the previous studies such as placent [45] and hepatic I/R (ischaemia-reperfusion) [14]. The activation of MAPK/NF- κ B pathway plays a crucial role in many aspects of immune mediated inflammatory responses [46].…”