Effect of Allium senescens Extract on Sorafenib Resistance in Hepatocarcinoma Cells

Abstract

Although Allium species are involved in bioactivity, to the best of our knowledge, there is no research on the effects of Allium senescens on drug resistance in hepatocarcinoma. Ultra-high performance liquid chromatography was used to determine the concentration of several bioactive compounds in A. senescens extract; flow cytometry, reverse transcription-quantitative polymerase chain reaction, and siRNA-mediated knockdown to estimate the levels of different markers in HepG2 cells. The quantity of p-coumaric acid in the extract was 4.7291 +/- 0.06 mu g/mL, and the protein of relevant evolutionary and lymphoid interest (PRELI) in the resistant cells decreased 2.1 times in the presence of p-coumaric acid. The resistant cells strongly downregulated the efflux transporters (ABCB1, ABCC2, and ABCG2) when exposed to the extract or p-coumaric acid and when PRELI was knocked down, in contrast to the influx proteins (OCT-1). Additionally, the extract induced mitochondrial apoptosis and suppressed autophagy. Consequently, the extract and p-coumaric acid attenuated drug resistance of HepG2 cells through the downregulation of PRELI, a key protein associated with the modulation of drug transporter expression, the activation of autophagy, and mitochondrial apoptosis. Our results indicate that A. senescens extract is beneficial in protecting cancer cells against drug resistance and sustaining the efficacy of sorafenib against liver cancer.