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Abstract Title:

Thymoquinone chemosensitizes human colorectal cancer cells to imatinib via uptake/efflux genes modulation.

Abstract Source:

Clin Exp Pharmacol Physiol. 2021 Mar 29. Epub 2021 Mar 29. PMID: 33783002

Abstract Author(s):

Nadia A Thabet, Dalia El-Khouly, Mohamed M Sayed-Ahmed, Mervat M Omran

Article Affiliation:

Nadia A Thabet

Abstract:

Imatinib (IM) is a pharmaceutical drug that inhibits tyrosine kinase enzymes that are responsible for the activation of many proteins by signal transduction cascades as c-Abl, c-Kit and the platelet-derived growth factor (PDGF) receptor. Thymoquinone (TQ) is an active constituent of Nigella sativa seeds. Thymoquinone benefits are attributed to its medicinal uses as antioxidant, anticancer and antimicrobial agent. This study aimed to investigate the impact of using TQ with IM in the HCThuman colorectal cancer cell line model. The HCTcells were treated with IM or/and TQ in non-constant ratios, in which the fixed concentrations of TQ (5, 10 or 20 µmol/L) were co-treated with various concentrations of IM (7.5-120 µmol/L) for 24, 48 and 72 hours. Imatinib-TQ interaction was analysed using CompuSyn software. The ICvalues for IM were 105, 72 μmol/L after 48 and 72 hours, respectively, and were significantly reduced to 7.3, 7 and 5.5 μmol/L after combination with TQ (10 μmol/L) and to 5.8, 5.6 and 4.6 μmol/L after combination with TQ (20 μmol/L) to 24, 48 and 72 hours, respectively. The combination index (CI) and dose reduction index (DRI) values indicate a significant synergism in HCT-116 cells at different treatment time points. Thymoquinone significantly enhances the cellular uptake of IM in HCTcells in a time and concentration-dependent manner. A significant downregulation in ATP-binding cassette (ABC) subfamily B member 1 (ABCB1), ABC subfamily G member 2 (ABCG2) and human organic cation transporter 1 (hOCT1) genes was observed in the cells exposed to IM+TQ combination as compared to IM alone, which resulted in a substantial elevation in uptake/efflux ratio in combination group. In conclusion, TQ potentiates IM efficacy on HCTcells via uptake/efflux genes modulation.

Study Type : In Vitro Study

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Sayer Ji
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