Retracted: The Natural Flavonoid Naringenin Inhibits the Cell Growth of Wilms Tumor in Children by Suppressing TLR4/NF-κB Signaling


Дәйексөз келтіру

Толық мәтін

Аннотация

Background: Nuclear Factor-kappa B (NF-κB) is usually activated in Wilms Tumor (WT) cells and plays a critical role in WT development.

Objective:The study's purpose was to screen for a NF-κB inhibitor from the natural product library and explore its effects on WT development.

Methods: Luciferase assay was employed to assess the effects of natural chemicals on NF-κB activity. CCK-8 assay was conducted to assess cell growth in response to naringenin. WT xenograft model was established to analyze the effect of naringenin in vivo. Quantitative real-time PCR and Western blot were performed to examine the mRNA and protein levels of relative genes, respectively.

Results: Naringenin displayed a significant inhibitory effect on NF-κB activation in SK-NEP-1 cells. In SKNEP- 1 and G-401 cells, naringenin inhibited p65 phosphorylation. Moreover, naringenin suppressed TNF-α- induced p65 phosphorylation in WT cells. Naringenin inhibited TLR4 expression at both mRNA and protein levels in WT cells. CCK-8 staining showed that naringenin inhibited cell growth of the two above WT cells in doseand time-dependent manner, whereas Toll-Like Receptor 4 (TLR4) overexpression partially reversed the above phenomena. Besides, naringenin suppressed WT tumor growth in a dose- and time-dependent manner in vivo. Western blot found that naringenin inhibited TLR4 expression and p65 phosphorylation in WT xenograft tumors.

Conclusion: Naringenin inhibits WT development via suppressing TLR4/NF-κB signaling.

Авторлар туралы

Hongtao Li

,

Хат алмасуға жауапты Автор.
Email: info@benthamscience.net

Peng Chen

,

Email: info@benthamscience.net

Lei Chen

,

Email: info@benthamscience.net

Xinning Wang

,

Email: info@benthamscience.net

Әдебиет тізімі

  1. (a)Chen, Y.; Williams, B.R. The role of NF-kappaB in the regulation of the expression of wilms tumor suppressor gene WT1. Gene Expr., 2000, 9(3), 103-114.doi: 10.3727/000000001783992614 PMID: 11243407 (b)Wang, Z.; Shao, M.; Liu, Y. Promotion of Wilms' tumor cells migration and invasion by mono-2-ethyhexyl phthalate (MEHP) via activation of NF-κB signals. Chem. Biol. Interact., 2017, 270, 1-8.doi: 10.1016/j.cbi.2017.04.004 PMID: 28390675
  2. Tang, F.; Zhang, H.; Lu, Z.; Wang, J.; He, C.; He, Z. Prognostic factors and nomograms to predict overall and cancer-specific survival for children with Wilms'. Tumor. Dis. Markers, 2019, 2019, 1092769.doi: 10.1155/2019/1092769 PMID: 31871495
  3. Davenport, K.P.; Blanco, F.C.; Sandler, A.D. Pediatric malignancies: Neuroblastoma, Wilm's tumor, hepatoblastoma, rhabdomyosarcoma, and sacroccygeal teratoma. Surg. Clin. North Am., 2012, 92(3), 745-767.doi: 10.1016/j.suc.2012.03.004 PMID: 22595719
  4. Cilloni, D.; Martinelli, G.; Messa, F.; Baccarani, M.; Saglio, G. Nuclear factor κB as a target for new drug development in myeloid malignancies. Haematologica, 2007, 92(9), 1224-1229.doi: 10.3324/haematol.11199 PMID: 17666366
  5. Aggarwal, B.B. Nuclear factor-kappaB: The enemy within. Cancer Cell, 2004, 6(3), 203-208.doi: 10.1016/j.ccr.2004.09.003 PMID: 15380510
  6. (a)Filho, J.C.; Sarria, A.L.; Becceneri, A.B.; Fuzer, A.M.; Batalhão, J.R.; da Silva, C.M.; Carlos, R.M.; Vieira, P.C.; Fernandes, J.B.; Cominetti, M.R. Copper (II) and 2,2′-bipyridine complexation improves chemopreventive effects of naringenin against breast tumor cells. PLoS One, 2014, 9(9), e107058.doi: 10.1371/journal.pone.0107058 PMID: 25192075 (b)Kong, Y.; Feng, Z.; Chen, A.; Qi, Q.; Han, M.; Wang, S.; Zhang, Y.; Zhang, X.; Yang, N.; Wang, J.; Huang, B.; Zhang, Q.; Xiang, G.; Li, W.; Zhang, D.; Wang, J.; Li, X. The Natural flavonoid galangin elicits apoptosis, pyroptosis, and autophagy in glioblastoma. Front. Oncol., 2019, 9, 942.doi: 10.3389/fonc.2019.00942 PMID: 31612107 (c)Raji, M.; Chen, Z. Effects of abiotic elicitors on the production of bioactive flavonols in Emilia sonchifolia. STEMedicine, 2020, 1(2), e33.doi: 10.37175/stemedicine.v1i2.33
  7. Ekambaram, G.; Rajendran, P.; Magesh, V.; Sakthisekaran, D. Naringenin reduces tumor size and weight lost in N-methyl-N'-nitro-N-nitrosoguanidine-induced gastric carcinogenesis in rats. Nutr. Res., 2008, 28(2), 106-112.doi: 10.1016/j.nutres.2007.12.002 PMID: 19083396
  8. (a)Kanno, S.; Tomizawa, A.; Hiura, T.; Osanai, Y.; Shouji, A.; Ujibe, M.; Ohtake, T.; Kimura, K.; Ishikawa, M. Inhibitory effects of naringenin on tumor growth in human cancer cell lines and sarcoma S-180-implanted mice. Biol. Pharm. Bull., 2005, 28(3), 527-530.doi: 10.1248/bpb.28.527 PMID: 15744083 (b)Yen, H.R.; Liu, C.J.; Yeh, C.C. Naringenin suppresses TPA-induced tumor invasion by suppressing multiple signal transduction pathways in human hepatocellular carcinoma cells. Chem. Biol. Interact., 2015, 235, 1-9.doi: 10.1016/j.cbi.2015.04.003 PMID: 25866363
  9. (a)Liu, J.; Yao, J.; Zhang, J. Naringenin attenuates inflammation in chronic obstructive pulmonary disease in cigarette smoke induced mouse model and involves suppression of NF-κB. J. Microbiol. Biotechnol., 2018.PMID: 30609878 (b)Kumar, R.P.; Abraham, A. Inhibition of LPS induced pro-inflammatory responses in RAW 264.7 macrophage cells by PVP-coated naringenin nanoparticle via down regulation of NF-κB/P38MAPK mediated stress signaling. Pharmacol. Rep., 2017, 69(5), 908-915.doi: 10.1016/j.pharep.2017.04.002 PMID: 28624598
  10. (a)Liang, J.; Halipu, Y.; Hu, F.; Yakeya, B.; Chen, W.; Zhang, H.; Kang, X. Naringenin protects keratinocytes from oxidative stress injury via inhibition of the NOD2-mediated NF-κB pathway in pemphigus vulgaris. Biomed. Pharmacother, 2017, 92, 796-801.doi: 10.1016/j.biopha.2017.05.112 PMID: 28591691 (b)Ali, R.; Shahid, A.; Ali, N.; Hasan, S.K.; Majed, F.; Sultana, S. Amelioration of Benzoapyrene-induced oxidative stress and pulmonary toxicity by Naringenin in Wistar rats: A plausible role of COX-2 and NF-κB. Hum. Exp. Toxicol., 2017, 36(4), 349-364.doi: 10.1177/0960327116650009 PMID: 27206700
  11. Raza, S.S.; Khan, M.M.; Ahmad, A.; Ashafaq, M.; Islam, F.; Wagner, A.P.; Safhi, M.M.; Islam, F. Neuroprotective effect of naringenin is mediated through suppression of NF-κB signaling pathway in experimental stroke. Neuroscience, 2013, 230, 157-171.doi: 10.1016/j.neuroscience.2012.10.041 PMID: 23103795
  12. Fan, R.; Pan, T.; Zhu, A.L.; Zhang, M.H. Anti-inflammatory and anti-arthritic properties of naringenin via attenuation of NF-κB and activation of the heme oxygenase (HO)-1/related factor 2 pathway. Pharmacol. Rep., 2017, 69(5), 1021-1029.doi: 10.1016/j.pharep.2017.03.020 PMID: 28943290
  13. Xu, X.; Han, K.; Tang, X.; Zeng, Y.; Lin, X.; Zhao, Y.; Zhang, Z.; Cao, B.; Wu, D.; Mao, X. The ring finger protein RNF6 induces leukemia cell proliferation as a direct target of Pre-B-cell leukemia homeobox 1. J. Biol. Chem., 2016, 291(18), 9617-9628.doi: 10.1074/jbc.M115.701979 PMID: 26971355
  14. Ma, J.X.; Sun, Y.L.; Yu, Y.; Zhang, J.; Wu, H.Y.; Yu, X.F. Triptolide enhances the sensitivity of pancreatic cancer PANC-1 cells to gemcitabine by inhibiting TLR4/NF-κB signaling. Am. J. Transl. Res., 2019, 11(6), 3750-3760.PMID: 31312385
  15. Gong, Y.; Zou, B.; Chen, J.; Ding, L.; Li, P.; Chen, J.; Chen, J.; Zhang, B.; Li, J. Potential five-MicroRNA signature model for the prediction of prognosis in patients with Wilms tumor. Med. Sci. Monit., 2019, 25, 5435-5444.doi: 10.12659/MSM.916230 PMID: 31328722
  16. Liu, J.; Hua, R.X.; Fu, W.; Zhu, J.; Jia, W.; Zhang, J.; Zhou, H.; Cheng, J.; Xia, H.; Liu, G.; He, J. MYC gene associated polymorphisms and Wilms tumor risk in Chinese children: A four-center case-control study. Ann. Transl. Med., 2019, 7(18), 475.doi: 10.21037/atm.2019.08.31 PMID: 31700911
  17. Luo, X.; Deng, C.; Liu, F.; Liu, X.; Lin, T.; He, D.; Wei, G. HnRNPL promotes Wilms tumor progression by regulating the p53 and Bcl2 pathways. OncoTargets Ther., 2019, 12, 4269-4279.doi: 10.2147/OTT.S203046 PMID: 31213844
  18. (a)Zhou, L.; Qi, L.; Jiang, L.; Zhou, P.; Ma, J.; Xu, X.; Li, P. Antitumor activity of gemcitabine can be potentiated in pancreatic cancer through modulation of TLR4/NF-κB signaling by 6-shogaol. AAPS J., 2014, 16(2), 246-257.doi: 10.1208/s12248-013-9558-3 PMID: 24424498 (b)Liu, L.; Li, Y.H.; Niu, Y.B.; Sun, Y.; Guo, Z.J.; Li, Q.; Li, C.; Feng, J.; Cao, S.S.; Mei, Q.B. An apple oligogalactan prevents against inflammation and carcinogenesis by targeting LPS/TLR4/NF-κB pathway in a mouse model of colitis-associated colon cancer. Carcinogenesis, 2010, 31(10), 1822-1832.doi: 10.1093/carcin/bgq070 PMID: 20400476
  19. Hao, X.; Gao, L.Y.; Zhang, N.; Chen, H.; Jiang, X.; Liu, W.; Ao, L.; Cao, J.; Han, F.; Liu, J. Tac2-N acts as a novel oncogene and promotes tumor metastasis via activation of NF-kappaB signaling in lung cancer. J. Experim. Clin. Cancer Res. CR (East Lansing Mich.), 2019, 38(1), 319.PMID: 31466523
  20. (a)Liao, A.C.; Kuo, C.C.; Huang, Y.C.; Yeh, C.W.; Hseu, Y.C.; Liu, J.Y.; Hsu, L.S. Naringenin inhibits migration of bladder cancer cells through downregulation of AKT and MMP-2. Mol. Med. Rep., 2014, 10(3), 1531-1536.doi: 10.3892/mmr.2014.2375 PMID: 25017119 (b)Dou, W.; Zhang, J.; Sun, A.; Zhang, E.; Ding, L.; Mukherjee, S.; Wei, X.; Chou, G.; Wang, Z.T.; Mani, S. Protective effect of naringenin against experimental colitis via suppression of Toll-like receptor 4/NF-κB signalling. Br. J. Nutr., 2013, 110(4), 599-608.doi: 10.1017/S0007114512005594 PMID: 23506745
  21. (a)Hsu, R.Y.; Chan, C.H.; Spicer, J.D.; Rousseau, M.C.; Giannias, B.; Rousseau, S.; Ferri, L.E. LPS-induced TLR4 signaling in human colorectal cancer cells increases beta1 integrin-mediated cell adhesion and liver metastasis. Cancer Res., 2011, 71(5), 1989-1998.doi: 10.1158/0008-5472.CAN-10-2833 PMID: 21363926 (b)Ehsan, N.; Murad, S.; Ashiq, T.; Mansoor, M.U.; Gul, S.; Khalid, S.; Younas, M. Significant correlation of TLR4 expression with the clinicopathological features of invasive ductal carcinoma of the breast. Tumour Biol., 2013, 34(2), 1053-1059.doi: 10.1007/s13277-013-0645-y PMID: 23338716 (c)Hsiao, C.C.; Chen, P.H.; Cheng, C.I.; Tsai, M.S.; Chang, C.Y.; Lu, S.C.; Hsieh, M.C.; Lin, Y.C.; Lee, P.H.; Kao, Y.H. Toll-like receptor-4 is a target for suppression of proliferation and chemoresistance in HepG2 hepatoblastoma cells. Cancer Lett., 2015, 368(1), 144-152.doi: 10.1016/j.canlet.2015.08.004 PMID: 26276725
  22. Zhang, Q.Q.; Zhou, D.L.; Ding, Y.; Liu, H.Y.; Lei, Y.; Fang, H.Y.; Gu, Q.L.; He, X.D.; Qi, C.L.; Yang, Y.; Lan, T.; Li, J.C.; Gong, P.; Wu, X.Y.; Yang, X.; Li, W.D.; Wang, L.J. Andrographolide inhibits melanoma tumor growth by inactivating the TLR4/NF-κB signaling pathway. Melanoma Res., 2014, 24(6), 545-555.doi: 10.1097/CMR.0000000000000117 PMID: 25244079
  23. Zhang, Q.Q.; Ding, Y.; Lei, Y.; Qi, C.L.; He, X.D.; Lan, T.; Li, J.C.; Gong, P.; Yang, X.; Geng, J.G.; Wang, L.J. Andrographolide suppress tumor growth by inhibiting TLR4/NF-κB signaling activation in insulinoma. Int. J. Biol. Sci., 2014, 10(4), 404-414.doi: 10.7150/ijbs.7723 PMID: 24719558
  24. Zhang, D.; Li, Y.H.; Mi, M.; Jiang, F.L.; Yue, Z.G.; Sun, Y.; Fan, L.; Meng, J.; Zhang, X.; Liu, L.; Mei, Q.B. Modified apple polysaccharides suppress the migration and invasion of colorectal cancer cells induced by lipopolysaccharide. Nutr. Res., 2013, 33(10), 839-848.doi: 10.1016/j.nutres.2013.06.004 PMID: 24074742

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