Chloroquine exacerbates serum withdrawal-induced G1 phase arrest: Via an autophagy-independent mechanism

Abstract

Chloroquine (CQ) is a widely used anti-malaria or complementary drug in the clinic. However, its effect on ischemic endothelial cells remains unclear. Herein, we showed that serum withdrawal induced G1 phase arrest and autophagy in human umbilical vein endothelial cells. Moreover, CQ exacerbated serum withdrawal-induced G1 phase arrest, whereas autophagy inhibition by Atg5 knockdown did not. Pathway analyses of Akt and MEK1/2/ERK1/2 verified the cell cycle difference between CQ and Atg5 knockdown. Additionally, CQ also exacerbated serum withdrawal-induced G1 phase arrest in the cells with Atg5 knockdown. Through employing glutathione, a reactive oxygen species scavenger, we confirmed that CQ-enhanced intracellular oxidative stress during serum withdrawal aggravated G1 phase arrest. We thus demonstrate that CQ exacerbates serum withdrawal-induced G1 phase arrest via an autophagy-independent, but an oxidative stress-dependent mechanism in endothelial cells.