Upregulation and activation of p53 by erastin ‑induced reactive oxygen species contribute to cytotoxic and cytostatic effects in A549 lung cancer cells.

Upregulation and activation of p53 by erastin‑induced reactive oxygen species contribute to cytotoxic and cytostatic effects in A549 lung cancer cells. Oncol Rep. 2018 Jul 20;: Authors: Huang C, Yang M, Deng J, Li P, Su W, Jiang R Abstract The tumour‑suppressor protein p53 is a key regulator of multiple cellular processes and exerts its tumour‑suppressor function by inducing apoptotic cell death. However, emerging evidence indicates that p53 is also involved in inducing ferroptosis, which is a unique iron‑dependent form of non‑apoptotic cell death triggered by the RAS‑selective lethal small molecule erastin. Previous studies have shown that erastin exposure induces increased ROS accumulation and oxidative stress. In the present study, we incubated A549 cells with erastin and detected ROS accumulation. Semi‑quantitative western blotting was performed to analyse the effect of the induced ROS on p53 activity. To determine how ROS activate p53, NAC, an ROS scavenger, and KU‑55933, an ATM kinase inhibitor, were employed to co‑incubate with erastin, followed by western blot analysis. Either p53 or SLC7A11 siRNA was introduced into A549 cells to silence the target‑gene expression, followed by ROS detection to illustrate the regulatory role of ROS‑activated p53 on its target gene SLC7A11. Annexin V‑FITC/PI staining was performed to detect the induction of apoptotic cell death by erastin exposure. To further assess th...
Source: Oncology Reports - Category: Cancer & Oncology Tags: Oncol Rep Source Type: research