Helenalin-induced apoptosis is dependent on production of reactive oxygen species and independent of induction of endoplasmic reticulum stress in renal cell carcinoma

Abstract

Helenalin, a sesquiterpene lactone, exhibits anti-inflammatory and anti-tumor activities. Here, we inves- tigated whether helenalin could induce apoptosis in human renal carcinoma Caki cells. Helenalin increased apoptosis in dose dependent manner in Caki cells, and also induced apoptosis in other carci- noma cells, such as human renal carcinoma ACHN cells, human colon carcinoma HT29 and HCT116 cells. We found that helenalin markedly induced endoplasmic reticulum (ER) stress-related genes, such as reg- ulated in development and DNA damage responses (REDD) 1, activating transcription factor-4 (ATF4) and/or the CCAAT enhancer-binding protein-homologous protein (CHOP). However, down-regulation of ATF4 and/or CHOP expression by siRNA had no effect on helenalin-induced apoptosis in Caki and HCT116 cells. Helenalin increased production of intracellular reactive oxygen species (ROS). Furthermore, ROS scavengers, N-acetylcystine (NAC), and glutathione ethyl ester (GEE), reduced helenalin-induced apoptosis. Taken together, helenalin induced apoptosis via ROS generation in human renal carcinoma Caki cells. Keywords: Helenalin ROS CHOP ATF4 Apoptosis Bcl-2