Identification of profilin 1 as the primary target for the anti-cancer activities of Furowanin A in colorectal cancer.

Furowanin A (Fur A) is a flavonoid compound isolated from medicinal plant Millettia pachycarpa Benth. This study aims to explore the effect of Fur A on Colorectal cancer (CRC) and its molecular mechanisms.Cell proliferative capacity of CRC cells was assessed by CCK-8 assay. Cell apoptosis and cell cycle distribution were detected by flow cytometry. Cell migration and invasion were detected by wound healing and Transwell assay, respectively. EMT markers, apoptosis and profilin 1(Pfnl) expression were detected by immunohistochemistry (IHC). The protein expression levels were examined by western blotting. i-TRAQ analyses were conducted to identify the differentially expressed genes in CRC cells. CRC xenograft model was also used to validate the in vivo anti-cancer activity of Fur A.Fur A exhibited anti-prolifertive, blocked cell cycle progression and promoted apoptotic cell death in CRC cells. Fur A suppressed the migration, invasion and epithelial-to-mesenchymal transition (EMT) in vitro, and tumor growth and pulmonary metastasis in vivo, without causing obvious toxicity. iTRAQ analysis identified Pfnl as a gene up-regulated by Fur A. In xenograft tumor tissue, the expression of Pfnl was also elevated by Fur A treatment. In clinical CRC samples, high expression of Pfnl was correlated with lower stage and longer survival. Knockdown of Pfnl significantly dampened the pro-apoptotic and anti-metastatic activities of Fur A in CRC cells. Ectopic Pfnl expression augmented the antineoplastic activities of Fur A.Fur A exhibited anti-cancer activities in vitro and in vivo in CRC by up-regulating Pfnl.