Antiproliferative, genotoxic activities and quantification of extracts and cucurbitacin B obtained from Luffa operculata (L.) Cogn

Abstract

The medicinal plant Luffa operculata (L.) Cogn. has therapeutic properties in the treatment of sinusitis, rhinitis and abortifacient conditions. Ethnopharmacological studies report that the antitumor potential can be attributed to the presence of cucurbitacin-like compounds in the plant. This study consisted of measuring cucurbitacin in different L. operculata extracts, evaluating the antiproliferative and genotoxic activity of the extracts and the isolated substance in gastric cancer cells line, and evaluating the possible mechanism of action. The extracts were obtained by maceration, and both the acquisition of the chemical profile of the extracts and the determination of cucurbitacin were performed by high-performance liquid chromatography (HPLC). For the isolation of cucurbitacin B, column chromatography was used, and molecular identification was carried out by Nuclear Magnetic Resonance (NMR). The MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay evaluated the antiproliferative activity, and the genotoxic activity was determined by the micronucleus method with cytokinesis blocking. The investigation of the possible mechanism of action was carried out by molecular docking. All tested samples caused cell death in a dose-dependent manner, but the fruit extracts were more selective for the ACP02 gastric cancer cells line than the isolated substance. The micronucleus results did not show that genomic instability reflects the greater cytotoxicity of the fruit ethanoic extract (EEF). In addition, the EEF proved to be the most selective for ACP02. The docking results showed that the isolated substance favorably inhibited the Janus kinase family proteins JAK1 and JAK2. The present work demonstrated that the use of ethanol extract can be a good alternative to fight gastric cancer.