Anti-Neoplastic Activity of Tetrahydrocurcumin in Liver Cancer by Modulating FOXO1/Parkin Tumour Suppressor Genes through In-Silico and In-Vitro Approaches

Liver Cancer (LC) is the greatest prevalent malignancy and the 2^nd factor for cancer death in worldwide. However, various conventional treatment strategies are unable to mitigate tumour recurrence and metastasis causes of poor prognosis and pose a major setback to improving the global survival rate of LC patients. As a consequence, there is a need to develop alternative strategies to improve the treatment of LC by utilizing phytocompounds. Tetrahydrocurcumin (THC) is a bio-oral available curcumin derivative derived from Curcuma longa. To assess the anti-cancer properties of THC by regulation of FOXO1 and Parkin, we have conducted several in-silico and in-vitro approaches. The results obtained in current studies, FOXO1 and Parkin gene expression as a tumour suppressor in LC were analysed by GEPIA 2 and UALCAN databases. THC had better pharmacokinetic characteristics and a higher binding affinity with FOXO1 and Parkin (-6.4 and -5.7 kcal/mol, respectively) than 5-fluorouracil. The IC₅₀ value for THC against HepG2 LC cells was 88.89 µM by MTT assay, showing that THC significantly reduced the cellular replication of LC cells gradually in a concentration-dependent way, whereas DNA fragmentation assay inspected that THC induces apoptosis of HepG2 LC cells. Subsequently, THC also up regulates FOXO1 and down regulates Parkin protein levels as revealed by in-vitro ELISA method. The inference from these findings was that THC potently restored the tumour suppression activities of FOXO1 and Parkin that were lost during tumour development. However, the current study has proven the therapeutic potential of THC in the halting the proliferation and enhancing the cell death in LC cells by regulating the protein levels of FOXO1/Parkin. Hence, this pre-clinical assessment would be a way forward in developing a neo-adjuvant therapy for LC patients that might enhance their survival rate in a safer way.