Wogonin reversed resistant human myelogenous leukemia cells via inhibiting Nrf2 signaling by Stat3/NF-κB inactivation
Authors: Li Zhao
Zhiyu Li
Xiaobo Zhang
Yicheng Liu
Lin Yang
Shaoliang Huang
Yi Zhang
Xuefen Xu
Lu Lu
Qinglong Guo
Lingyi Kong
Journal: Scientific Reports (2017)
Discipline: Multidisciplinary
Keywords: Nrf2; Wogonin; Chemoresistance; NF-κB; Stat3
Affiliations: State Key Laboratory of Natural Medicines, Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China., State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing, 210009, People's Republic of China.

Abstract:  Constitutive NF-E2-related factor 2 (Nrf2, NFE2L2) activation has been recently reported to play a pivotal role in enhancing cell survival and resistance to anticancer drugs in many tumors. Wogonin had strong reversal potency via reduction of Nrf2 mRNA in Adriamycin (ADR)-induced resistant human chronic myelogenous leukemia (CML) K562/A02, but the mechanism of reduction of Nrf2 mRNA was still unclear. In this study, we aimed to delineate the mechanism by which Wogonin suppressed transcription of Nrf2 in resistant CML cells and further evaluate the reversal effects of Wogonin on the established animal models. Data indicated that Wogonin suppressed transcription of Nrf2 by NF-κB inactivation. Wogonin inhibited the binding of p65 to Nrf2 by suppression of the κB-binding activity. Further research revealed the κB2 site was responsible for the decreased Nrf2 by Wogonin in resistant K562 cells. Furthermore, reduction of pY705-Stat3 was involved in inhibition of the binding of p65 to Nrf2 by Wogonin. In vivo, Wogonin potentiated the inhibitory effect of ADR on leukemia development by suppressing pY705-Stat3 and Nrf2 signaling. In summary, these results demonstrated Wogonin could combat chemoresistance effectively through inhibiting Nrf2 via Stat3/NF-κB signaling, and supported that Wogonin can be developed into an efficient natural sensitizer for resistant human myelogenous leukemia. 

Retracted: No

PubPeer comments:
 2020 Expression of Concern. https: www.jbc.org content 295 26 8876 The publisher of the Journal of Biological Chemistry is issuing an Expression of Concern to inform readers that credible concerns have been raised regarding some of the data and conclusions in the article listed above. The Journal of Biological Chemistry will provide additional information as it becomes available. , 
 Retraction on Jan 1, 2021, published online May 22, 2021 https: www.jbc.org article S0021-9258(21)00556-1 fulltext Withdrawal: Bone marrow stromal cell-derived growth inhibitor inhibits growth and migration of breast cancer cells via induction of cell cycle arrest and apoptosis This article has been withdrawn by the authors except the first author Tao Wang, who could not be reached. The Journal states that in Fig. 3A, the first two lanes in the BDGI immunoblot, corresponding to MCF-7 and MCF-7 mock, were identical. The withdrawing authors state that they disagree with the Journalu2019s findings. The withdrawing authors state that this study was conducted nearly 20 years ago. The age of the work and the lack of availability of data storage makes it difficult for the authors to retrieve the requested raw data. The withdrawing authorsu2019 offer to replace the image in question with that from another experiment with the same condition was declined by the Journal. The withdrawing authors state that the above issue does not affect the interpretation of the data nor conclusions of this research study. This article describes the discovery of a novel molecule, BDGI, and its functional characterization as an inhibitor of growth and migration in breast cancer. The withdrawing authors state that its function and mechanism have been confirmed in breast cancer and other types of cancer by other independent studies. The withdrawing authors have indicated that they plan to resubmit their findings elsewhere for publication. ,