Abstract 16P
Background
Imatinib (IM) is a pharmaceutical drug that inhibits tyrosine kinases enzymes which are responsible for the activation of many proteins by signal transduction cascades as c-Abl, c-Kit and the PDGF receptor. Thymoquinone (TQ) is an active constituent of Nigella Sativa seeds. TQ benefits are attributed to its medicinal uses as antioxidant, anticancer and antimicrobial agent. It also possesses anti-inflammatory and hepatoprotective effects. This study aimed to investigate the chemo-modulatory potential of TQ to IM in colon cancer cells (HCT-116).
Methods
Colon cancer cell line (HCT-116) was treated with different concentrations (7.5-120 μM) of IM and/or TQ for 24, 48, 72 h. Cytotoxic and apoptotic potentials of combination therapy were carried out using different techniques. IM-TQ interaction was analyzed using compusyn software.
Results
Our data showed that TQ synergistically augments the cytotoxic activity of IM in HCT-116 cells. The IC50 values for IM were significantly reduced to 7.3, 7 and 5.5 μM after combination with (10 μM) TQ and to 5.8, 5.6 and 4.6 μM after combination with (20 μM) TQ for 24, 48 and 72 h. The CI and DRI values indicate a significant synergism in HCT-116 cells at 24, 48 and 72 h of treatment. The combination of IM with 5 μM TQ showed a marginal effect after 24 and 48 h of treatment, but after 72 h of treatment TQ enhances cytotoxicity of IM on HCT-116 cells. Further investigation by using flow cytometry and real time PCR analysis showed that the TQ sensitized HCT-116 cells to IM therapy. TQ induced apoptotic effect of IM via down regulation of anti-apoptotic BCL-2 (P=0.004) and BCL-XL(P=0.01) and upregulation of tumor suppressor PAR-4 (P=0.002) and BAX(P<0.001).
Conclusions
The current data demonstrates the promising role of Thymoquinone in potentiate chemotherapeutic effects of Imatinib on colon cancer cells.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.