8-bromo-7-methoxychrysin targets NF-Œ∫B and FoxM1 to inhibit lung cancer stem cells induced by pro-inflammatory factors
Authors: Jian-Guo Cao
Chang Xu
Zhen-Wei Song
Min Wen
Ye-Bei Qiu
Qing Yuan
Jian-Song Zhang
A Chen
Journal: Journal of Cancer (2019)
Discipline: CLINICAL MEDICINE
Keywords: FoxM1; NF-Œ∫B; cancer stem cell; inflammatory factor; lung cancer
Affiliations: Department of preclinical medicine, Medical College, Hunan Normal University, Changsha, 410013, China., Department of Pharmaceutical Science, Medical College, Hunan Normal University, Changsha, 410013, China.

Abstract:  We have previously reported that 8-bromo-7-methoxychrysin (BrMC), a novel synthetic derivative of chrysin, was demonstrated anti-tumor activities against several human cancers, including lung cancer. Interaction between inflammation and cancer stem cell are recently increasingly recognized in tumorigenesis and progression. The purpose of this study was to investigate whether BrMC inhibits lung cancer stemness of H460 cells induced by inflammatory factors (TGF-Œ≤ combined with TNF-Œ±) and its potential mechanism. Our results showed that BrMC inhibited lung cancer stemness, as validated by enhanced self-renewal ability, higher in vitro tumorigenicity, and increased expression of CD133, CD44, Bmi1 and Oct4 in H460 cells administered TNF-Œ± after prolonged induction by TGF-Œ≤, in a concentration-dependent manner. Both NF-Œ∫B inhibition by SN50 and FoxM1 suppression by thiostrepton (THI) prompted the inhibition of BrMC on lung CSCs. Conversely, overexpression of NF-Œ∫Bp65 significantly antagonized the above effects of BrMC. Meanwhile, overexpression of FoxM1 also significantly compromised BrMC function on suppression of FoxM1 and NF-Œ∫Bp65 as well as stemness of lung CSCs. Our results suggest that activation of NF-Œ∫B and FoxM1 by cytokines facilitate the acquisition CSCs phenotype, and compromise the chemical inhibition, which may represent an effective therapeutic target for treatment of human lung cancer. Moreover, BrMC may be a potential promising candidate for targeting NF-Œ∫B/ FoxM1 to prevent the tumorigenesis under inflammatory microenvironment. 

Retracted: No

PubPeer comments:
 Two sets of images seem to overlap between Figures 3 and 5, although they seem to be described differently. I was unable to locate email addresses for the authors in this paper. ***  *** Acknowledgements. This study was funded by the Projects of NSFC (No.30760248, No.81172375 and No.31400311), the Project of Scientific Research Fund of Hunan Provincial Education Department (No.14C0707), the Project of Hunan Provincial Natural Science Foundation (No.13JJ3061) and the Scientific Research Fund of Hunan Normal University (No.140668). This project also received financial support from Health and Family Planning Commission of Hunan Province (No. B2016091) and Open Grant of Key Laboratory of Study and Discovery of Small Targeted Molecules of Hunan Province (2019CG01). , 
 Some bands in Figure 1K and 2K appear quite similar, although they appear to have been edited differently. Could the authors please provide the original raw data showing the intact gel images? I m assuming that the journal will eventually provide me with the email addresses as I have requested. ***  , 
 Figure 3K (right side): the same actin control (rescaled) was used also in [Wen et al. 2019](http: pubpeer.com publications B82D2C1D7C0AC3526C8C3656D3646A) where cell lines used and treatments performed were different.  , 
 Figure 1K (right side): the same actin control appears in Figure 5a of [Cao et al. 2019](http: pubpeer.com publications 3C5C46FEACD080022838634215301A) **(retracted paper)**.  , 
 #3 Figure 3k (right) again: blots taken from other papers where the conditionsand or description were different  , 
 Figure 2k (left side): the **Oct4** panel is the same blot published four years before by an unrelated group in Figure 5a of ***Lin et al. 2015 PLOS One 0(5): e0123305*** (the latter does NOT seem to be problematic), where it was described as **EGFR**. [Aided by ImageTwin sofware]  ,