Abstract
Nigella sativa seeds, which are also known as black cumin or black seed, contain a bioactive substance called thymoquinone (TQ). It has garnered attention due to its potential health benefits. TQ is a natural substance that has the potential to be beneficial due to its anti-platelet and anti-cancer properties. We can attribute its anti-cancer effects to its capacity to prevent platelet activation and aggregation, as well as to promote platelet apoptosis. Despite the fact that the exact processes underlying thymoquinone’s anti-platelet and anti-cancer effects remain unclear, a number of studies have provided insight into the subject. However, no research has investigated the mechanisms causing TQ’s direct impact on platelet-induced cancer spread. The purpose of this study was to examine the effect of TQ-pretreated platelets on platelet-induced MDA-MB-231 metastasis in vitro. The results demonstrate that TQ effectively inhibits platelet-cell adhesion (53.38% ± 5.69%), reducing platelet-induced migration by about 50% and transmigration of MDA-MB231 cells by 36% ± 9.4%. Additionally, 10 µM TQ suppresses MDA-MB231 cell-induced the protein tyrosine phosphorylation in platelets as well as Btk activation by 45% ± 6.7%. 10 µM TQ and LFMA13 have the capacity to suppress ZEB2 expression to 73% ± 2.8%, increase the expression of FBXW7, β-catenin 1 to 147% ± 4.33% and 136% ± 5.3%, respectively, and decrease vimentin (38% ± 3%) and N-cadherin (29% ± 4%) expression, and prevent platelet-induced transmigration. The findings demonstrate that TQ suppresses both the platelet-inducing epithelial-to-mesenchymal transition (EMT) and MDA-MB231 cells transmigration through mediating the FBXW7-ZEB2-β-catenin signaling pathway and downregulating Bruton’s tyrosine kinase (Btk).