Aminoquinolines as Translational Models for Drug Repurposing: Anticancer Adjuvant Properties and Toxicokinetic-Related Features

Table 1

General mechanisms of chemosensitizing and radiosensitizing adjuvant actions of chloroquine, hydroxychloroquine, and analogues.

Treatment/Drug	Adjuvant actions	References
Phosphatidylinositol analogs, oligopeptides Akt-PH linkers, inhibitors of Akt-kinase, and blockers of ATP-binding site catalytic subunit	Mediated chemosensitization and enhanced cytotoxicity	[50]
All-trans retinoic acid	Reduction of Ki67-positive cells and clonogenicity, activation of histone acetyltransferase, and inhibition of histone deacetylase enzymes	[51]
5-Fluorouracil	Down-regulation of CDK-2 expression and cyclin E/CDK2 complex activity, arrest in G0/G1 phase, and enhancement of antiproliferative properties	[52]
Everolimus	Proliferative reduction, increase of p53 and p21^Cip1 levels, phosphorylation reduction at serine 2448 in mTOR proteins	[48]
Rapamycin	Blockade of autophagy and LC3-II degradation, cytotoxic chemosensitization and involvement of a caspase-independent mechanism	[53]
Cisplatin	Increase of caspase-3 activation, LC3 II ubiquitinated intracellular misfolded proteins, and intrinsic apoptosis	[54, 55]
Docetaxel	Enhanced cytotoxicity and stronger in vivo anti-tumor efficacy	[56]
Doxorubicin	Potentiated cytotoxicity upon coexposure	[57]
Oxilaplatin	Increased sensitivity under hypoxic conditions and p62 levels, delaying of tumor growth of HT-29 colon cancer xenografts	[58]
Sunitinib	Increase of the p62 level, reduction of blood vessel formation, CD-34 expression, microvessel density, and nitric oxide levels in tumor, and Ehrlich ascites carcinoma tumor growth reduction	[59]
Temozolomide	Cell viability reduction and intensification of cleaved-caspase-3, cleaved-PARP1, phosphatidylserine externalization, and caspase-3/7 activation	[54, 60]
Receptor-interacting protein kinase 3 (RIP3)	Upregulation of RIP3, accumulation of RIP3-p62 complexes and type II-LC3B, and efficiency on colon tumor-bearing mice	[61]
Bevacizumab	Weakening of the Akt-mTOR signaling pathway and recovering the tumor-suppressive effect of bevacizumab	[62]
Sertraline + erlotinib	Amplification of caspase-independent autophagic cell death and mouse survival in orthotopic non-small cell lung cancer mouse models	[63]