Therapeutic potential of liposome@azoramide in cancer by suppressing oxidative phosphorylation.

OBJECTIVE

Targeting cancer cell metabolism represents a promising therapeutic strategy; however, metabolic reprogramming in tumor cells complicates the effectiveness of therapies aimed at disrupting these pathways.

METHODS

This study explored the potential of Azoramide, a compound previously associated with enhanced insulin sensitivity, to modulate cancer metabolism. Azoramide-loaded nano-liposomes (Lip@Azo) were prepared via the thin-film hydration method, chosen for its simplicity and efficiency. We evaluated the anti-tumor efficacy of Lip@Azo and investigated the underlying mechanisms.

RESULTS

We showed that azoramide effectively inhibits tumor growth by suppressing oxidative phosphorylation (OXPHOS) both in vitro and in vivo. Azoramide downregulated OXPHOS proteins, reduced mitochondrial respiration, and induced reactive oxygen species (ROS), leading to decreased mitochondrial ATP generation. Additionally, azoramide downregulated PGC-1α, a key regulator of mitochondrial function, disrupting mitochondrial homeostasis and further impairing tumor cell metabolism, which induced apoptosis and ferroptosis in cancer cells. To enhance the solubility and delivery of azoramide, we encapsulated the compound in liposomes (Lip@Azo), which significantly improved its therapeutic efficacy in vivo.

CONCLUSION

Overall, our findings suggest that Lip@Azo is a promising strategy for targeting mitochondrial metabolism in cancer, offering a new avenue for therapeutic development in oncology.