Abstract

Continuous obstacles behind the discovery of novel drugs for cancer therapy have necessitated the development of alternative strategy of drug repurposing—the development of old drugs for new therapeutic purposes. With an improved understanding of the hallmarks of cancer, this strategy offers a cost-effective process for the treatment of human neoplastic disease, thereby facilitating rapid clinical translation. In this regard, macrolide antibiotics (MAs), which include a wide spectrum of activities against Gram-positive bacteria, have also been proposed as anticancer drugs for multiple tumor types. Over the past few years, significant progress has been achieved in anticancer therapy, but development of resistance and unavoidable side effects have weakened these attainments. Considering this severe condition, a number of drugs with novel antitumor mechanisms are under investigations including antimicrobials that have been shown to possess anti-inflammatory, immunomodulatory, and cytotoxic effects. In this regard, both conventional and novel antimicrobials are being studied to explore their anticancer potential along with underlying mechanisms that may render them as effective anticancer drugs in the future. Hence, in the latest study, we tested the role of a macrolide antibiotic drug, Azithromycin (AZM) alone, in combination with standard chemotherapeutic agent Sorafenib (Sorafenib/AZM) and its gold conjugated nanoparticles (AuAZM) as an anti angiogenic agent in hepatoma cell line hepG2 through wound healing assay. The migratory potential of HepG2 cells after being exposed to different treatments (AZM, Sorafenib, Sorafenib/AZM, and Au-AZM at IC50 concentrations) was observed at 0, 6, 24, 48, and 72 hours. The results of our study showed that AZM exhibited highly significant reduction in wound healing with p-value (< 0.001) up till 72 hours, while Sorafenib, Sorafenib/AZM, and Au-AZM inhibited wound healing up to 48 hours (p-value < 0.001). The current study revealed a comparatively higher antiangiogenic potential of AZM in cancer cells, thereby suggesting its clinical application for cancer treatment.

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