Re-sensitization of cancer multidrug resistance through P-gp, MRP1 and BCRP modulation: advances in terpenoids based cancer therapy

Among the most significant risks that many chemotherapeutic drugs currently encounter is the development of multidrug resistance (MDR) in cancerous cells. Numerous critical regulators are thought to be responsible for MDR and render therapeutic strategies inefficient. Several pathways mediate this effect, one of which is the upregulation of ATP-binding cassette (ABC) superfamily membrane transporters. Most of these transporters, which regarded as drug efflux pumps, are embedded in the cell membrane and include MDR-associated protein 1 (MRP1/ABCC1), MRP2, P-glycoprotein (MDR1/ABCB or P-gp), and breast cancer resistance protein (BCRP/ABCG2). The exploration of new potential modulators to diminish tumor MDR through natural product-derived compounds has emerged as a prominent research domain worldwide. Among different plant-derived natural compounds, terpenoids have recently attracted attention owing to their extensive health advantages. Multiple preclinical findings have primarily explored plant-derived terpenoids for their MDR-modulatory activities. Plant-based terpenoids counteract MDR by modulating signaling pathways or expression of pertinent proteins or genes. Thus, this review summarizes preclinical experimental data to elucidate the functional roles of terpenoids in MDR reversal by targeting ABC transporters and sheds light on future research on terpenoid-based cancer therapy.