The potential impact of trigonelline loaded micelles on Nrf2 suppression to overcome oxaliplatin resistance in colon cancer cells

Nuclear factor erythroid 2-related factor 2 (Nrf2) has a pivotal role in promoting chemoresistance by regulation of antioxidants and detoxification enzymes. Trigonelline is one of the major alkaloids in raw coffee which has been recently introduced as potent inhibitor of Nrf2. This study investigated the role of trigonelline and trigonelline loaded micelles in Nrf2 inhibition to break down oxaliplatin resistance in colon cancer cells. The PCL-PEG-PCL and PLA-PCL-PEG-PCL-PLA copolymers and trigonelline loaded micelles were prepared and characterized for fourier transforms infrared (FTIR), hydrogen nuclear magnetic resonance ( 1 H-NMR), carbon nuclear magnetic resonance ( 13 C-NMR) spectroscopy, particle size, zeta potential, scanning electron microscopy (SEM) and entrapment efficiency. Cell viability and apoptosis were evaluated by using MTT and flow cytometry assays, respectively. Nrf2, MRP1, NQO1, HO-1, Bax, and Bcl2 gene expressions were examined by qRT-PCR. Our results revealed that micelles had spherical shapes with narrow sizes and zeta potential indexes of − 9.06 ± 6.94 mV for trigonelline loaded 3Block and − 7.47 ± 6.08 mV for trigonelline loaded 5Block micelles. After Nrf2 inhibition by trigonelline, antioxidant response element (ARE) related gene expressions were decreased (p