Turmerone-loaded nanocarriers effectively induced apoptosis and attenuated cancerous phenotype inin vitroandin vivoHCC models.

[BACKGROUND] Hepatocellular carcinoma (HCC) still has a high mortality rate and an increasing prevalence trend. Therefore, improving treatment methods is essential for the management of this cancer. Turmerones, which are the main volatile natural components of Curcuma longa Linn, have shown a number of beneficial biological activities both in vitro and in vivo. However, because of their hydrophobicity, their delivery methods need substantial improvement. Niosomes, which are made of non-ionic surfactants, have shown promising results in drug delivery systems (DDSs). Due to their appropriate encapsulation rate, stability, bioavailability, and predictable release patterns, they could be useful tools in DDSs. In this study, we demonstrated the benefit of treatment with turmerone-loaded niosomes on cancerous phenotypes of two HCC cell line in vitro and in vivo.

[METHOD] Turmerone-loaded niosomes were synthesized through thin-film hydration method and characterized with dynamic light scattering (DLS), scanning electron microscopy (SEM), and Fourier transform infrared (FTIR). The impact of turmerone-loaded niosomes on Huh-7 and Hep3B cells were assessed in vitro in term of gene expression, protein production, apoptosis, cell cycle, and some functional assessments such as colony formation potential and migration. Furthermore, tumorigenesis potential of the turmerone-loaded niosomes treated hepatoma cells was assessed in an in vivo model using nude mice.

[RESULTS] Our in vitro experiments showed that turmerone-loaded niosomes induced apoptosis (26.04 % for Huh-7 and 29.7 % for Hep3B) and cell cycle arrest in Huh-7 and Hep3B cells. Additionally, turmerone-loaded niosomes treatment down-regulated EMT-inducing genes and significantly decreased the EMT phenotype, as well as decreased colony formation capacity in both cell lines (surviving fraction of 0.27 for Huh-7 and 0.032 for Hep3B). In vivo study showed that upon transplantation, hepatoma cells which have been pre-treated with turmerone-loaded niosomes have less growth rate and produced smaller tumors with significantly few proliferating cells in nude mice.

[CONCLUSION] This study showed that turmerone delivery through niosome have higher anti-cancer potentials in comparison to free-turmerone treatment on HCC cell line. Therefore, this approach could have a promising therapeutic potential in combination with other approved clinical settings for HCC treatment.