Iron oxide-silver-curcumin nanocomposite acts against HPV16 positive cervical cancer cell siha by triggering crosstalk between autophagy and apoptosis primarily via breach in cellular redox equilibrium

Curcumin, the dietary phytocompound obtained from Curcuma sp. possesses multiple bioactivities of which its appreciable anti-tumour activity has been evidenced pertaining to cytotoxicity mediated through different cell death pathways. However, hydrophobicity of this molecule poses a major hindrance as it directly affects bioavailability and thus anti-tumor property. Currently, cervical cancer is one of the most commonly occurring women cancers worldwide and is a growing menace especially in the developing countries. In this study we have tried to formulate a novel green-synthesised iron oxide-silver nanocomposite-based delivery system for curcumin so as to improve its druggability against the HPV-16 positive cervical cancer cell line SiHa. Different microscopic, flow cytometric, spectrophotometric and immunoblotting assays were used to analyse its effects on the targeted cells. We have observed that the curcumin-nanocomposite showed enhanced anti-proliferative capability compared to free curcumin against SiHa showing increased cellular uptake at 24 h treatment. Further, it modulated the PI3K/AKT/mTOR signalling cascade to induce both autophagic and apoptotic death in the target cells. Such changes were mainly orchestrated through imbalance in intracellular redox system and resultant augmented ROS accumulation. Our study suggests that this bimetallic nanocomposite can aid in increasing bioavailability and concomitant therapeutic efficacy of curcumin.

Automated summary

In this study, a novel green-synthesized iron oxide-silver nanocomposite-based delivery system for curcumin was developed to improve its druggability against the HPV-16 positive cervical cancer cell line SiHa. The curcumin-nanocomposite showed enhanced anti-proliferative capability compared to free curcumin, with increased cellular uptake at 24 h treatment. It modulated the PI3K/AKT/mTOR signaling cascade to induce both autophagic and apoptotic death in the target cells, mainly through imbalance in intracellular redox system and resultant augmented ROS accumulation. This study suggests that this bimetallic nanocomposite can increase bioavailability and therapeutic efficacy of curcumin.