Effects of thymoquinone and thymoquinone-loaded nanostructured lipid carrier on hepatocellular carcinoma cell models, Hep3B and HepG2

Hepatocellular carcinoma (HCC) is the fourth most common solid tumor. Dysregulated cell proliferation and tumorigenesis of HCC is commonly associated with chronic hepatitis B infection. Thymoquinone (TQ), a bioactive compound found in Nigella sativa has been shown to exhibit anti-tumor properties. However, due to some limitations of discomfort, high cost and sterility, it was synthesized into Thymoquinone-loaded nanostructured lipid carrier (TQ-NLC) (PATENT NO: PI2012001818) to improve the bioavailability and cytotoxicity of TQ. As cellular models for in vitro liver cancer and toxicity studies, HepG2 and Hep3B are the two most frequently used liver cancer cells. This study aims to determine the differential effects of TQ and TQ-NLC on the different genomic sequence of liver cancer (Hep3B and HepG2 cell lines) as well as to identify the molecular mechanisms underlying its anticancer activities. TQ or TQ-NLC inhibited the growth of both models of human liver cancer cells. The IC50 obtained for Hep3B treated TQ or TQ-NLC at 24 hours was 16.7±2.86 μM and 13.5±3.58 μM respectively. While in HepG2 treated TQ or TQ-NLC at 24 hours, the IC50 obtained was 47.7±0.64 μM and 24.0±0.70 μM respectively. TQ-NLC was observed to be more toxic towards Hep3B cells with IC50 of 9.20 ± 2.25 μM compared to TQ with IC50 of 11.1 ± 0.41 μM at 72 hours of treatment. Meanwhile, IC50 of Hepg2 treated TQ-NLC was 25.5 ± 8.40 μM compared to TQ which was 41.8 ± 6.20 μM at 72 hours of treatment. Overall treatment showed both TQ and TQ-NLC were more toxic towards liver cancer cells compared to normal 3T3 with IC50 >30uM (P