Anti-invasive effect and pharmacological mechanism of genistein against colorectal cancer

Colorectal cancer (CRC) refers to a deadly carcinoma following potent invasiveness and metastasis in advanced stage. Unfortunately, existing anti-CRC medicine is insufficient for chemotherapy in addition to adverse effects. Consequently, the candidate natural ingredient for treating CRC needs to be further developed. Our previous experiments report that genistein exerts beneficial effects to inhibit CRC cells via an antiproliferative mechanism. Based on the metastatic characteristics of staging CRC, anti-invasive and antimetastatic pharmacological activities using genistein remain uninvestigated. The scientific purpose of this study was to disclose the antimetastatic mechanism by using human and cell culture/nude mice samples, followed by biochemical tests and immunoassays. In human study, these CRC cases resulted in increased transforming growth factor beta-1 (TGF-beta 1) levels, long noncoding RNA (lncRNA) TTTY18 expressions, followed with up-regulated Ki-67, serum and glucocorticoid regulated kinase 1 (SGK1), Akt(Ser473) expressions. In a study in vitro, genistein-dosed CRC cells showed suppressed cell viability, promoted cell apoptosis, reduced Ki-67 positive cells, reduced cellular migration, down-regulated expressions of TTTY18, SGK1, Akt(Ser473), p38 MAPK(Tyr323). In a further study in vivo, genistein-dosed tumor-bearing nude mice exhibited visibly reduced body mass, lowered tumorous TGF-beta 1 and TTTY18 contents. In addition, intracellular numbers of SGK1, Akt(Ser473), p38 MAPK(Tyr323) positive cells were reduced dose-dependently. Collectively, these human and experimentative findings reveal that genistein pharmacologically exerts the potential antimetastatic CRC effects, possibly through a molecular mechanism of inhibiting TTTY18/Akt pathway in CRC cells.