Does chloroquine induce autophagy?

Does chloroquine induce autophagy?

Chloroquine (CQ), an antimalarial agent, is able to induce sustained endoplasmic reticulum (ER) stress by functioning as an autophagy inhibitor. The present study indicated that CQ had the ability to induce apoptosis in QBC939 cholangiocarcinoma cells.

How does chloroquine affect autophagy?

Chloroquine (CQ), which is frequently used clinically as an antimalarial agent, is a classic inhibitor of autophagy that blocks the binding of autophagosomes to lysosomes by altering the acidic environment of lysosomes, resulting in the accumulation of a large number of degraded proteins in cells (8).

What does chloroquine do to lysosomes?

Research studies demonstrate that chloroquine accumulates in acidic lysosomes and increases the lysosomal pH. This inhibits lysosomal hydrolases and prevents autophagosomal fusion and degradation, which can result in apoptotic or necrotic cell death (1-4).

How does hydroxychloroquine inhibit autophagy?

CQ and HCQ can inhibit autophagy by blocking the fusion of autophagosomes with lysosomes. In addition, CQ also has some autophagy-independent anticancer effects, including sensitizing cancer cells to chemotherapy. Several related clinical trials have been conducted to evaluate the safety and value of it.

How does chloroquine accumulate in lysosomes?

The unprotonated form of chloroquine preferentially accumulates in lysosomes as it rapidly diffuses across cell/organelle membranes. Once in the lower pH (4.6), environment of the lysosome chloroquine becomes protonated and can no longer freely diffuse out (16).

How is autophagy measured?

One of the most common ways to monitor autophagy is by measuring the protein levels of LC3-II, which is incorporated into autophagosomes and then degraded in the lysosome. There are many different ways to measure LC3 protein levels, including western blot and immunofluorescent microscopy2.

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