Corynoxine Inhibits Tumor Growth via Targeting NQO1 and Modulating the PTPA–NQO1/PP2A Switch to Activate PP2A
- 1School of Medicine Taizhou University Taizhou Zhejiang China
- 2The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital Zhengzhou Henan China
- 3Department of Basic Medicine and Medical Laboratory Science School of Medicine Zhejiang Key Laboratory of New Drug Development for Central Nervous System Diseases Taizhou University Taizhou Zhejiang China
Abstract
Corynoxine (Cory) has been reported to suppress lung cancer progression by activating PP2A, but its molecular targets remain unclear. This study shows that Cory exerts anticancer activity across multiple cancer cell lines. Using compound derivatization, affinity‐based protein fishing, LC‐MS/MS, SPR, CETSA, DARTS, and molecular docking, we demonstrate that Cory directly interacts with NQO1, with Gly193 and His194 contributing to ligand recognition. NQO1 is overexpressed and implicated in tumor progression in multiple cancers, although its precise mechanisms remain poorly defined. We identified a previously unrecognized interaction between NQO1 and PTPA that may contribute to PP2A suppression in tumor cells. Cory binding perturbs the NQO1–PTPA interface and weakens their cellular association, thereby facilitating PTPA‐dependent PP2A activation. This activation inhibits the PI3K/AKT and MAPK/ERK pathways and suppresses tumor cell proliferation. Critically, Cory's anticancer effects are abolished in NQO1‐deficient cells, highlighting the essential role of NQO1. Cory did not impair NQO1 enzymatic activity, supporting a non‐enzymatic mechanism. In vivo, Cory suppressed tumor growth in nude mice without obvious systemic toxicity. Collectively, these findings suggest that Cory exerts anticancer effects by modulating the PTPA–NQO1/PP2A switch to activate PP2A, positioning Cory as a promising lead compound for targeted therapy.
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BibTeX
@article{hou2026corynoxine,
title = {{Corynoxine Inhibits Tumor Growth via Targeting NQO1 and Modulating the PTPA–NQO1/PP2A Switch to Activate PP2A}},
author = {Guoqing Hou and Li Lin and Mengjie Xia and Ruohan Liang and Yueyue Zhang and Linna Du and Xuan Cao},
journal = {Advanced Science},
year = {2026},
month = aug,
doi = {10.1002/advs.77362},
url = {https://doi.org/10.1002/advs.77362},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Corynoxine Inhibits Tumor Growth via Targeting NQO1 and Modulating the PTPA–NQO1/PP2A Switch to Activate PP2A
AU - Guoqing Hou
AU - Li Lin
AU - Mengjie Xia
AU - Ruohan Liang
AU - Yueyue Zhang
AU - Linna Du
AU - Xuan Cao
PY - 2026
DA - 2026/08/20
JO - Advanced Science
DO - 10.1002/advs.77362
UR - https://doi.org/10.1002/advs.77362
AB - Corynoxine (Cory) has been reported to suppress lung cancer progression by activating PP2A, but its molecular targets remain unclear. This study shows that Cory exerts anticancer activity across multiple cancer cell lines. Using compound derivatization, affinity‐based protein fishing, LC‐MS/MS, SPR, CETSA, DARTS, and molecular docking, we demonstrate that Cory directly interacts with NQO1, with Gly193 and His194 contributing to ligand recognition. NQO1 is overexpressed and implicated in tumor progression in multiple cancers, although its precise mechanisms remain poorly defined. We identified a previously unrecognized interaction between NQO1 and PTPA that may contribute to PP2A suppression in tumor cells. Cory binding perturbs the NQO1–PTPA interface and weakens their cellular association, thereby facilitating PTPA‐dependent PP2A activation. This activation inhibits the PI3K/AKT and MAPK/ERK pathways and suppresses tumor cell proliferation. Critically, Cory's anticancer effects are abolished in NQO1‐deficient cells, highlighting the essential role of NQO1. Cory did not impair NQO1 enzymatic activity, supporting a non‐enzymatic mechanism. In vivo, Cory suppressed tumor growth in nude mice without obvious systemic toxicity. Collectively, these findings suggest that Cory exerts anticancer effects by modulating the PTPA–NQO1/PP2A switch to activate PP2A, positioning Cory as a promising lead compound for targeted therapy.
SN - 2198-3844
ER -