Abstract
Introduction:
Hepatocellular carcinoma (HCC) remains one of the most predominant types of digestive system malignancies worldwide. TNF-related apoptosis-inducing ligand (TRAIL) is a biological cytokine with the mentioned specificity, but some tumor cells' resistance limits its use as a therapeutic approach. The present study aimed to investigate thymoquinone (TQ) and TRAIL's combined effect and the potential mechanisms in human hepatic HepG2 carcinoma cells.
Methods:
Cell viability and IC50 dose for TQ and TRAIL, alone and in combination, were determined using the MTT method. ELISA evaluated the expression levels of 8-Hydroxy-2'-deoxyguanosine. The apoptosis rate was assessed by flow cytometry, ELISA cell death assay, and caspase 8 activity assays. The mRNA and protein evaluation of candidate genes, including survivin, Bcl-2, XIAP, c-IAP1, c-IAP2, and c-FLIP, were accomplished before and after the treatment using qRT-PCR and Western blot analysis, respectively.
Results:
Our results showed that TQ synergistically increased TRAIL's cell toxic effects as follows: TQ plus TRAIL > TRAIL > TQ. TQ could sensitize the HepG2 cells against the TRAIL-induced apoptosis and amplify the caspase 8 activity. This outcome is achieved by decreasing the mRNA and protein expression levels of anti-apoptotic genes.
Conclusions:
Our findings suggest that TQ can sensitize the human HCC cell line HepG2 against TRAIL by inducing the death receptor pathway. Moreover, these agents' combinational therapy might promise a therapeutic regimen for improving the clinical efficacy of TRAIL-induced apoptosis in patients with HCC.
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