West Asia Organization for Cancer Prevention (WAOCP), APOCP's West Asia Chapter. Asian Pacific Journal of Cancer Prevention 1513-7368 15 6 2014 06 01 Luteolin Sensitizes Two Oxaliplatin-Resistant Colorectal Cancer Cell Lines to Chemotherapeutic Drugs Via Inhibition of the Nrf2 Pathway 2911 2916 29018 EN Journal Article 1970 01 01 Oxaliplatin is a first-line therapy for colorectal cancer, but cancer cell resistance to the drug compromisesits efficacy. To explore mechanisms of drug resistance, we treated colorectal cancer cells (HCT116 and SW620)long-term with oxaliplatin and established stable oxaliplatin-resistant lines (HCT116-OX and SW620-OX).Compared with parental cell lines, IC50s for various chemotherapeutic agents (oxaliplatin, cisplatin anddoxorubicin) were increased in oxaliplatin-resistant cell lines and this was accompanied by activation of nuclearfactor erythroid-2 p45-related factor 2 (Nrf2) and NADPH quinone oxidoreductase 1 (NQO1) . Furthermore,luteolin inhibited the Nrf2 pathway in oxaliplatin-resistant cell lines in a dose-dependent manner. Luteolin alsoinhibited Nrf2 target gene [NQO1, heme oxygenase-1 (HO-1) and GSTα1/2] expression and decreased reducedglutathione in wild type mouse small intestinal cells. There was no apparent effect in Nrf2-/- mice. Luteolincombined with other chemotherapeutics had greater anti-cancer activity in resistant cell lines (combined indexvalues below 1), indicating a synergistic effect. Therefore, adaptive activation of Nrf2 may contribute to thedevelopment of acquired drug-resistance and luteolin could restore sensitivity of oxaliplatin-resistant cell linesto chemotherapeutic drugs. Inhibition of the Nrf2 pathway may be the mechanism for this restored therapeuticresponse. https://journal.waocp.org/article_29018_13b4cdc9c6f7fbdc3c596e104acf3d15.pdf