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Article Publish Status: FREE
Abstract Title:

Curcumol Overcomes TRAIL Resistance of Non-Small Cell Lung Cancer by Targeting NRH:Quinone Oxidoreductase 2 (NQO2).

Abstract Source:

Adv Sci (Weinh). 2020 Nov ;7(22):2002306. Epub 2020 Oct 15. PMID: 33240775

Abstract Author(s):

Jing Zhang, Ye Zhou, Nan Li, Wan-Ting Liu, Jun-Ze Liang, Yue Sun, Wei-Xia Zhang, Run-Dong Fang, Sheng-Ling Huang, Zheng-Hua Sun, Yang Wang, Qing-Yu He

Article Affiliation:

Jing Zhang

Abstract:

Resistance to tumor-necrosis-factor-related apoptosis-inducing ligand (TRAIL) of cancer cell remains a key obstacle for clinical cancer therapies. To overcome TRAIL resistance, this study identifies curcumol as a novel safe sensitizer from a food-source compound library, which exhibits synergistic lethal effects in combination with TRAIL on non-small cell lung cancer (NSCLC). SILAC-based cellular thermal shift profiling identifies NRH:quinone oxidoreductase 2 (NQO2) as the key target of curcumol. Mechanistically, curcumol directly targets NQO2 to cause reactive oxygen species (ROS) generation, which triggers endoplasmic reticulum (ER) stress-C/EBP homologous protein (CHOP) death receptor (DR5) signaling, sensitizing NSCLC cell to TRAIL-induced apoptosis. Molecular docking analysis and surface plasmon resonance assay demonstrate that Phe178 in NQO2 is a critical site for curcumol binding. Mutation of Phe178 completely abolishes the function of NQO2 and augments the TRAIL sensitization. This study characterizes the functional role of NQO2 in TRAIL resistance and the sensitizing function of curcumol by directly targeting NQO2, highlighting the potential of using curcumol as an NQO2 inhibitor for clinical treatment of TRAIL-resistant cancers.

Study Type : In Vitro Study
Additional Links
Pharmacological Actions : Chemotherapeutic : CK(2328) : AC(1086)

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