Spirogyra neglecta (Hassall) Kützing attenuates metastasis of castration-resistant human prostate cancer via the blockage of AKT signaling pathway

Spirogyra neglecta (Hassall) Kützing, a filamentous fresh water green alga, has clearly demonstrated its anti-inflammation properties; however, the anti-metastasis activity of this plant has not yet been elucidated. This study aimed to investigate the anti-metastasis effects of S. neglecta against castration-resistant prostate cancer cells. Transwell assays were used to determine the anti-metastasis properties of S. neglecta against PC3 cells. Furthermore, the metabolic profiling, 1H-NMR based metabolomics analysis, was conducted to identify the potential active compounds. The results revealed that S. neglecta ethanolic extract (SnEE) significantly inhibited PC3 cells invasion and migration. The metabolomics for the profiling-based screening of very well-known medicinal herbs in Asian countries (S. neglecta, S. platensis, T. erecta, C. siamea) have indicated a significant positive association between gallic acid, gentisic acid and the anti-metastasis properties of the SnEE. Thus, the solvent-partition technique was performed to concentrate the phenolic compounds in SnEE and then to establish the S. neglecta ethyl acetate fraction (SnEA). Mechanistically, SnEA inhibited PC3 cells metastasis through the inhibition of MMP-9 secretion, epithelial-mesenchymal transition, and the Akt signaling pathway (p<0.01). Our study, for the first time, showed that S. neglecta extract displayed remarkable anti-metastasis properties against castration-resistant prostate cancer by inhibiting the Akt signaling pathway. These findings appeared to support the use of S. neglecta extract as a natural supplement in the effective treatment of prostate cancer.