Antimetastatic Effects of Thymoquinone in Colorectal Cancer: Targeting Cell Adhesion, Migration, and Invasion in...

Thymoquinone (TQ), the major bioactive constituent of Nigella sativa, Asian and African medicinal plant, has attracted growing interest for its anticancer properties. In this study, we investigated the antimetastatic potential of TQ in human colorectal carcinoma (CRC) cell lines SW480 and SW620, representing primary and metastatic stages, respectively. The treatment with several concentration of TQ has significantly reduced cell adhesion to extracellular matrix proteins (fibronectin, collagen I and IV), without affecting adhesion to poly-l-lysine, proving disruption of integrin-mediated attachment. Furthermore, wound healing and transwell migration assays demonstrated that TQ has significantly inhibited CRC cell motility and migratory capacity in a time- and dose-dependent manner. Interestingly, our findings highlight the therapeutic potential of TQ in colorectal cancer by targeting tumor cell dissemination. Thus TQ may represent a promising candidate for the development of novel antimetastatic strategies as a nutraceutical compound in colorectal cancer therapy. Importantly, TQ treatment led to a marked, dose-dependent decrease in MMP9 and MMP2 mRNA expression, as revealed by RT-PCR and densitometric quantification. At the highest doses, MMP9 and MMP2 expression levels were reduced to 0.76- and 0.56-fold (SW480, 30 μM) and to 0.73- and 0.61-fold (SW620, 48 μM) relative to control, respectively. These findings demonstrate that TQ robustly inhibits the transcription of key metastasis-associated markers in CRC cells.