Dissecting pharmacological effects of chloroquine in cancer treatment: interference with inflammatory signaling pathways

Abstract

Chloroquines are 4-aminoquinoline-based drugs mainly used to treat malaria. At pharmacological concentrations, they have significant effects on tissue homeostasis, targeting diverse signaling pathways in mammalian cells. A key target pathway is autophagy, which regulates macromolecule turnover in the cell. In addition to affecting cellular metabolism and bioenergetic flow equilibrium, autophagy plays a pivotal role at the interface between inflammation and cancer progression. Chloroquines consequently have critical effects in tissue metabolic activity and importantly, in key functions of the immune system. In this article, we will review the work addressing the role of chloroquines in the homeostasis of mammalian tissue, and the potential strengths and weaknesses concerning their use in cancer therapy.

Chloroquine against malaria, cancers and viral diseases

“…Despite considerable evidence for the efficacy and safety of CQ, the mechanisms behind its antitumor effects remain unclear. CQ not only impairs the anticancer immune response and prevents tumor cell escape [44] , but also has advantages in regulating multiple cellular signaling pathways involved in inflammation and cancer [45] compared with other important natural agents, such as curcumin [46] , zerumbone [47] , thymoquinone [48] , and honokiol [49] . It can affect the expression level of inflammatory factors, including nuclear factor-kappa B (NF-κB) and interleukin-1 beta (IL-1β).…”

Guide to Immunopharmacology: a database to boost immunology education, research and therapy

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Combining Nelfinavir With Chloroquine InhibitsIn VivoGrowth of Human Lung Cancer Xenograft Tumors

“…Chloroquine, an anti-malarial lysosomotropic drug, inhibits autophagy by increasing lysosomal pH and preventing autophagosome-lysosome fusion (4). Chloroquine also represents a prominent case of drug repurposing for cancer therapy against glioblastoma, MM, breast cancer, pancreatic cancer, etc.…”