Preparative isolation and purification of steroidal glycoalkaloid from the ripe berries of Solanum nigrum L. by preparative HPLC-MS and UHPLC-TOF-MS/MS and its anti-non-small cell lung tumors effects in vitro and in vivo

Abstract

Overcoming epidermal growth factor receptor resistance is a critical problem that needs to be solved in clinical practice. Drugs that downregulate the fatty acid synthase-epidermal growth factor receptor will become novel treatments for non-small cell lung cancer. Solanum nigrum, extracted with water at 4°C, shows strong cytotoxic activity and inhibits tumor growth in Lewis tumor bearing-mice in a dose-dependent manner. A novel active compound in S. nigrum, solaoiacid, was successfully separated and purified from S. nigrum by preparative high-performance liquid chromatography with mass spectrometry and ultra high performance liquid chromatography with time-of-flight tandem mass spectrometry. The IC₅₀ of solaoiacid on lung cancer cells was 2.3 µmol/L, which was significantly lower than that of the known steroidal glycoalkaloid. Label-free proteomics and STRING Network analysis were used to identify significantly deregulated proteins in lung cancer cells that were treated with the fresh ripe fruit extracts of S. nigrum. S. nigrum regulates multiple signal pathways, including the epidermal growth factor receptor pathway. S. nigrum downregulated 24 main proteins with direct roles in fatty acid biosynthesis. Both S. nigrum and solaoiacid showed strong downregulation of the fatty acid synthase-epidermal growth factor receptor and anti-non-small cell lung cancer effects, and thus will become a novel drug for the treatment of non-small cell lung cancer.

Keywords: Solanum nigrum berries; epidermal growth factor receptor; fatty acid synthase; non-small cell lung cancer; proteomics.