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.