RESUMO
N-methylsansalvamide (SA), one of cyclic pentadepsipeptides produced by several Fusarium strains, is a promising therapeutic agent for the treatment of cancer disease. In order to make sufficient amount of SA for drug development, a green and efficient extraction process of SA from the mycelia of strain Fusarium sp. R1 using deep eutectic solvent-assisted ultrasound extraction (DES-UAE) was firstly achieved in this work. Solvent screening results indicated that choline chloride-acetic acid (ChCl-Aa) was shown to be the best DES for SA extraction. Through single-factor trials, Plackett-Burman design (PBD) and BoxBehnken design (BBD) experiments, the optimal conditions for DES-UAE with the highest SA yield of 58.2 ± 1.1 mg/g were obtained as follows: ChCl-Aa ratio of 1:2.0 (M/M), water content of 16.4 %, liquid-solid ratio of 37:1 (mL/g), ultrasonic power of 175 W for 47.4 min at 46.3 °C. Compared to conventional extraction approaches, DES-UAE exhibited better SA yield since it caused more serious damage to the surface of mycelia powder on basis of scanning electron microscopy (SEM) analysis. Furthermore, molecular interaction studies suggested that SA has a variety of interactions with ChCl-Aa, including hydrogen and electrovalent bonds as well as van der Waals forces. Finally, the recovery rate of SA reached up to 99.5 % when the ratio of distilled water and DES extracts was 15:1 (V/V). These findings provide the way for large-scale production of SA.
RESUMO
N-methylsansalvamide (MSSV), a cyclic pentadepsipeptide, was obtained from a strain of Fusarium solani f. radicicola. The current study investigated the anti-colorectal cancer effect of MSSV. MSSV exhibited the inhibition of the proliferation in HCT116 cells via induction of G0/G1 cell cycle arrest by downregulating CDK 2, CDK6, cyclin D, and cyclin E, and upregulating p21WAF1 and p27KIP1. Decreased phosphorylation of AKT was observed in MSSV-treated cells. Moreover, MSSV treatment induced caspase-mediated apoptosis through elevating the level of cleaved caspase 3, cleaved PARP, cleaved caspase 9, and pro-apoptotic Bax. MSSV revealed the declined MMP-9 level mediated by reduction in the binding activity of AP-1, Sp-1, and NF-κB motifs, which led to the migration and invasion of HCT116 cells. In vitro metabolism with rat liver S9 fractions was performed to examine the effect of MSSV metabolites. The metabolic process enhanced the inhibitory effect of MSSV on the HCT116 cell proliferation via decline of cyclin D1 expression and AKT phosphorylation. Finally, oral administration of MSSV inhibited the tumor growth of HCT116 xenograft mice. These results suggest that MSSV is a potential anti-tumor agent in colorectal cancer treatment.