Exploration of the antiproliferative and antioxidant effects and the molecular docking study EGFR and VEGFR2 of essential oil from Citrus aurantium Peels

Abstract

Cancer is a significant global health issue with high recurrence rates despite extensive treatments. Hence, the search for new anticancer treatments is of great importance. The purpose of this study was to assess the efficacy of Citrus aurantium peels essential oil (CPEO) as a potential anti-cancer treatment. The Full Factorial Design 23 method was employed to optimize the yield of CPEO extraction and to examine its antioxidant and antiproliferative effects on HeLa and MCF-7 cancer cell lines. GC-MS analysis revealed that limonene is the major constituent of CPEO (68.32%). The optimal extraction yield of 5.47 g/100 g d.b was achieved with a 4-minute microwave pretreatment, 5 washings, and a minimum salt concentration of 175 g/L. The CPEO was endowed with interesting antioxidant activity evaluated by DPPH, H2O2, NO•, assays with IC50 of 0.492; 1.120; 1.243 mg/mL respectively. In addition, CPEO exhibited powerful antiproliferative effects evaluated with the MTT assay against HeLa (IC50 of 0.650 μg/mL) and MCF-7 (IC50 of 1.426 μg/mL) cell lines. The statistical correlation analyses showed a positive relationship between the IC50 values for MCF-7 and HeLa with the total phenol content (TPC). Based on the molecular docking study, CPEO constituents could dock into the binding pockets of EGFR with energy between -1.695 and -5.052 kcal/mol, As for VEGFR2, energy ranged between -4.175 and -8.096 kcal/mol. Naphthalen-1(2h)-one, limonene, and citral showed an interesting inhibition capacity against EGFR and VEGFR2 by molecular docking study. These findings suggest that CPEO would be a potential natural therapeutic agent for cancer treatment.