Chloroquine has been extensively used in mass drug administrations, which may have contributed to the emergence and spread of resistance. It is recommended to check if chloroquine is still effective in the region prior to using it. Chloroquine treatment of cells Hydroxychloroquine fatigue The mechanism through which chloroquine is acting on cancer cells has mainly been attributed to the inhibition of autophagy as a consequence of its lysosomotropic properties 13, 24. Consistently, we also observed a strong inhibitory effect of chloroquine on autophagy in the established PDAC cell lines previously used in the cited studies. Chloroquine is a 9-aminoquinoline that has been known since 1934. Specifically synthesised to be used as an antimalarial agent, chloroquine was subsequently shown to have immunomodulatory properties that have encouraged its application in the treatment of autoimmune diseases such as rheumatoid arthritis. An important mode of action of chloroquine and hydroxychloroquine is the interference of lysosomal activity and autophagy. It is widely accepted that chloroquine and hydroxychloroquine accumulate. The Centers for Disease Control and Prevention recommend against treatment of malaria with chloroquine alone due to more effective combinations. In areas where resistance is present, other antimalarials, such as mefloquine or atovaquone, may be used instead. Chloroquine mechanism of action autophagy Chloroquine Modes of action of an undervalued drug., Effects of chloroquine on viral infections an old drug. Plaquenil and mctd Chloroquine has a long history of human use and is currently being tested as a sensitizing agent for certain cancers, making understanding its mechanisms of action both topical and important. Chloroquine is a lysosomotropic weak base, which in the monoprotonated form diffuses into the lysosome, where it becomes diprotonated and becomes trapped. Inhibition of autophagy with bafilomycin and chloroquine.. Mechanisms of action of hydroxychloroquine and chloroquine.. ER stress and autophagy new discoveries in the mechanism.. It has also been demonstrated that chloroquine sensitizes breast cancer cells to chemotherapy independent of autophagy inhibition, and the potential side effects of chloroquine therapy have also been cautiously discussed. This indicates that a more detailed understanding of chloroquine's anticancer mechanism is required in order to further develop this compound into an effective anticancer agent. Chloroquine's potential chemosensitizing and radiosensitizing activities in cancer may be related to its inhibition of autophagy, a cellular mechanism involving lysosomal degradation that minimizes the production of reactive oxygen species ROS related to tumor reoxygenation and tumor exposure to chemotherapeutic agents and radiation. In parallel with these findings, another study demonstrated that autophagy is a key mechanism for anti-leukemic effects of ATO in AML cell lines and leukemic progenitors from AML patients, and this induction of autophagy flux is associated with mitogen-activated protein kinase kinase MEK/extracellular signal-regulated kinase ERK-dependent autophagic cell death.