Chloroquine inhibits human retina pigmented epithelial cell growth and microtubule nucleation by downregulating p150 ^glued

Chloroquine (CQ) is an antimalaria drug that has been used in clinical practice for several decades. One serious complication of CQ treatment is the macular retinopathy caused by the disruption of the retinal pigmented epithelium, leading to vision loss. Little is known about how CQ affects retinal pigmented epithelium. In this study, we found that cell proliferation was reduced by CQ treatment in time and dose-dependent manners. No obvious cell death was detected; however, what was observed instead was G0/G1 arrest during which primary cilium started to grow in the presence of CQ. Pharmacological inhibition of primary cilium formation led to a reduction of cell viability suggesting that CQ-induced primary cilium protected cells from death. In addition to cell growth, with the CQ treatment the retina pigmented epithelium (RPE) cells less flattened with the spindle-like protrusion. When checking the microtubule networks, the microtubule nucleation activity was disrupted in the presence of CQ. The level of p150 ^glued , the largest subunit of dynactin, was reduced in CQ-treated RPE1 cells, and depletion of p150 ^glued resulted in a phenotype reminiscent of CQ-treated cells. Thus, CQ treatment reduced the expression of p150 ^glued , leading to reduced S phase entry and defective microtubule nucleation.