Chloroquine inhibits cell growth and induces cell death in A549 lung cancer cells.
To investigate the effects of chloroquine diphosphate (CQ) on lung cancer cell growth, we treated A549 cells, a lung cancer cell line, with the drug at various concentrations (0.25-128 microM) for 24-72 h. The results showed that, at lower concentrations (from 0.25 to 32 microM), CQ inhibited the growth of A549 cells and, at the same time, it induced vacuolation with increased volume of acidic compartments (VAC). On the other hand, at higher concentrations (64-128 microM), CQ induced apoptosis at 24 h, while its effect of inducing vacuolation declined. The lactate dehydrogenase (LDH) assay showed that with the treatment of CQ 32-64 microM for 72 h or 128 microM for 48 h, CQ induced necrosis of A549 cells. To understand the possible mechanism by which CQ acts in A549 cells, we further incubated the cells with this drug at the concentrations of 32 or 128 microM in the presence of D609, a specific inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC). The results showed that D609 (50 microM) could inhibit the effects of CQ 32 microM on the viability and VAC, but it could not change the effects of CQ 128 microM on the same. Our data suggested that CQ inhibited A549 lung cancer cell growth at lower concentrations by increasing the volume of lysosomes and that PC-PLC might be involved in this process. The data also indicated that, at higher concentrations, CQ induced apoptosis and necrosis, but at this time its ability to increase the volume of lysosome gradually declined, and PC-PLC might not be implicated in the process.
Fan
Chuandong
C
Institute of Developmental Biology, School of Life Science, Shandong University, Jinan 250100, China.
Wang
Weiwei
W
Zhao
Baoxiang
B
Zhang
Shangli
S
Miao
Junying
J
D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D048430:Cell Shape; D002738:Chloroquine / Q000494:pharmacology* / Q000633:toxicity; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*
D002738:Chloroquine