Co-targeting of lysosome and mitophagy in cancer stem cells with chloroquine analogues and antibiotics

The catabolic autophagy eliminates cytoplasmic components and organelles via lysosomes. Non-selective bulk autophagy and selective autophagy (mitophagy) are linked in intracellular homeostasis both normal and cancer cells. Autophagy has complex and paradoxical dual role in cancers; it can play either tumour suppressor or tumour promoter depending on the tumour type, stage, microenvironment and genetic context. Cancer stem cells (CSCs) cause tumour recurrence and promote resistant to therapy for driving poor clinical consequences. Thus, new healing strategies are urgently needed to annihilate and eradicate CSCs. As chloroquine (CQ) analogues show positive clinical outcome in several clinical trials either standalone or combination with several chemotherapies. Moreover, CQ analogues are known to eliminate CSCs via altering DNA methylation. However, several obstacles such as higher concentrations and dose-dependent toxicity are noticeable in the treatment of cancers. As tumour cells predominantly rely on mitochondrial actions, mitochondrial targeting FDA-approved antibiotics are reported to effectively eradicate CSCs alone or combination with chemotherapy. However, antibiotics cause metabolic glycolytic shift in cancer cells for survival and repopulation. This review will provide a sketch of the inhibiting roles of current chloroquine analogues and antibiotic combination in CSC autophagy process and discuss the possibility that pre-clinical and clinical potential therapeutic strategy for anticancer therapy.