New Use for Old Drugs? Prospective Targets of Chloroquines in Cancer Therapy

Abstract

During the last decade research is gradually repositioning the antimalarial drug chloroquine, and certain related quinoline derivatives, as anticancer agents. Chloroquine and hydroxychloroquine, in particular, have relatively well-characterized toxicity profiles due to several decades of use for treatment of malaria. Previously published review articles provide an excellent overview of the diversity of chloroquine effects on cancer cells, both in the cell culture as well as on human tumors grafted into mice; and an account of the increasing pace of incorporation of hydroxychloroquine in combination treatment schemes for clinical studies. In this review we present some features that are common between cancers that are sensitive to quinoline derivatives, in particular features that are amenable to pharmaceutical intervention.

Evaluation of cytotoxic activity of titanocene difluorides and determination of their mechanism of action in ovarian cancer cells

“…Defects in autophagy are associated with susceptibility to metabolic stress, genomic damage and tumorigenesis, indicating a role of autophagy in tumor suppression [37]. On the other hand, autophagy can promote the growth of established tumors [38] making autophagy process a double-edged sword [39,40]. Our results support the hypothesis that titanocenes may cause ER stress followed by autophagy induction.…”

The Antileishmanial Potential of C-3 Functionalized Isobenzofuranones against Leishmania (Leishmania) Infantum Chagasi

“…Conceivably, due to the intense replication of this parasite during acute infection, it could be strongly affected by DNA damage or free radicals. Indeed, reports in the literature have indicated that anti-cancer drugs that affect cellular proliferation can be used as anti-microbial agents because both cell types share common behaviors concerning their high proliferative capabilities [27][28][29]. Indeed, a recent work evidenced the antileishmanial actions of other two isobenzofuranone derivatives and indicated that these actions were due to the induction of reactive oxygen species (ROS)-mediated apoptosis-like cell death and the inhibition of topoisomerases [30].…”

Dynamic aberrant NF-κB spurs tumorigenesis: A new model encompassing the microenvironment

“…Inhibition of the proteasome [8], or epigenetic reprogramming via a deacetylase inhibitor [144], may lead to activation of homeostatic responses and NF-κB, and rescue a malignant cell from antineoplastic treatments. One such example is the induction of lysosome activity after inhibition of the proteasome: this is not only a trigger for lysosome-dependent degradation of IκB, but it can also result in rescue of the cancer cell through autophagy, which enables it to survive by recycling many of its contents [145]. It is therefore important to target therapeutic intervention to the drug-induced metabolic pathway that rescues the malignant cell.…”