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Article

Regulation of the FOXO3a/Bim signaling pathway by 5,7-dihydroxy-8-nitrochrysin in MDA-MB-453 breast cancer cells

  • Authors:
    • Xiao-Chun Zhao
    • Xiao-Cheng Cao
    • Fei Liu
    • Mei-Fang Quan
    • Kai-Qun Ren
    • Jian-Guo Cao
  • View Affiliations / Copyright

    Affiliations: Department of Oncology, First Affiliated Hospital of University of South China, Hengyang 421001, P.R. China, Laboratory of Medicine Engineering, Medical College, Hunan Normal University, Changsha 410013, P.R. China
  • Pages: 929-934
    |
    Published online on: December 14, 2012
       https://doi.org/10.3892/ol.2012.1077
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Abstract

We previously demonstrated that 5,7-dihydroxy-8-nitrochrysin (NOC), a novel synthetic chrysin analog, preferentially inhibits HER-2/neu-overexpressing MDA-MB‑453 breast cancer cell growth by inducing apoptosis; however, the precise molecular mechanism was unclear. In this study, we demonstrated that NOC significantly induces apoptosis of MDA-MB-453 cells and that this is primarily mediated through a mitochondrial death cascade. This was presented as a loss of mitochondrial membrane potential, release of cytochrome c and activation of caspase-9. NOC induces a significant increase in levels of the BH3-only protein Bim. Small interfering RNA-mediated knockdown of Bim markedly attenuated NOC-induced apoptosis. An upstream transcriptional regulator of Bim, forkhead box O3a transcription factor (FOXO3a), experienced a decrease in phosphorylation and nuclear translocation. Silencing of FOXO3a resulted in a marked attenuation in the expression of Bim, as well as protection against NOC-mediated apoptosis. Furthermore, NOC-induced activation and nuclear localization of FOXO3a was associated with reduced levels of Akt phosphorylation. These results suggest that NOC induces apoptosis in MDA-MB-453 human breast cancer cells via caspase activation and modulation of the Akt/FOXO3a pathway.
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1 

Jemal A, Siegel R, Ward E, et al: Cancer statistics, 2006. CA Cancer J Clin. 56:106–130. 2006. View Article : Google Scholar

2 

Qiu MZ, Xu RH, Ruan DY, et al: Incidence of anemia, leukocytosis, and thrombocytosis in patients with solid tumors in China. Tumour Biol. 31:633–641. 2010. View Article : Google Scholar : PubMed/NCBI

3 

Zhang T, Chen X, Qu L, Wu J, Cui R and Zhao Y: Chrysin and its phosphate ester inhibit cell proliferation and induce apoptosis in Hela cells. Bioorg Med Chem. 12:6097–6105. 2004. View Article : Google Scholar : PubMed/NCBI

4 

Lee SJ, Yoon JH and Song KS: Chrysin inhibited stem cell factor (SCF)/c-Kit complex-induced cell proliferation in human myeloid leukemia cells. Biochem Pharmacol. 74:215–225. 2007. View Article : Google Scholar : PubMed/NCBI

5 

Woo KJ, Jeong YJ, Park JW and Kwon TK: Chrysin-induced apoptosis is mediated through caspase activation and Akt inactivation in U937 leukemia cells. Biochem Biophys Res Commun. 325:1215–1222. 2004. View Article : Google Scholar : PubMed/NCBI

6 

Wang W, VanAlstyne PC, Irons KA, Chen S, Stewart JW and Birt DF: Individual and interactive effects of apigenin analogs on G2/M cell-cycle arrest in human colon carcinoma cell lines. Nutr Cancer. 48:106–114. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Zhang Q, Zhao XH and Wang ZJ: Flavones and flavonols exert cytotoxic effects on a human oesophageal adenocarcinoma cell line (OE33) by causing G2/M arrest and inducing apoptosis. Food Chem Toxicol. 46:2042–2053. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Kachadourian R, Leitner HM and Day BJ: Selected flavonoids potentiate the toxicity of cisplatin in human lung adenocarcinoma cells: a role for glutathione depletion. Int J Oncol. 31:161–168. 2007.PubMed/NCBI

9 

Saarinen N, Joshi SC, Ahotupa M, et al: No evidence for the in vivo activity of aromatase-inhibiting flavonoids. J Steroid Biochem Mol Biol. 78:231–239. 2001. View Article : Google Scholar : PubMed/NCBI

10 

Walle T, Otake Y, Brubaker JA, Walle UK and Halushka PV: Disposition and metabolism of the flavonoid chrysin in normal volunteers. Br J Clin Pharmacol. 51:143–146. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Zheng X, Meng WD, Xu YY, Cao JG and Qing FL: Synthesis and anticancer effect of chrysin derivatives. Bioorg Med Chem Lett. 13:881–884. 2003. View Article : Google Scholar : PubMed/NCBI

12 

Zhao XC, Tian L, Cao JG and Liu F: Induction of apoptosis by 5,7-dihydroxy-8-nitrochrysin in breast cancer cells: the role of reactive oxygen species and Akt. Int J Oncol. 37:1345–1352. 2010.PubMed/NCBI

13 

Gomes AR, Brosens JJ and Lam EW: Resist or die: FOXO transcription factors determine the cellular response to chemotherapy. Cell Cycle. 7:3133–3136. 2008. View Article : Google Scholar : PubMed/NCBI

14 

van Gorp AG, Pomeranz KM, Birkenkamp KU, Hui RC, Lam EW and Coffer PJ: Chronic protein kinase B (PKB/c-akt) activation leads to apoptosis induced by oxidative stress-mediated Foxo3a transcriptional up-regulation. Cancer Res. 66:10760–10769. 2006.PubMed/NCBI

15 

Essafi A, Fernandez de Mattos S, Hassen YA, et al: Direct transcriptional regulation of Bim by FoxO3a mediates STI571-induced apoptosis in Bcr-Abl-expressing cells. Oncogene. 24:2317–2329. 2005. View Article : Google Scholar : PubMed/NCBI

16 

Yang XH, Zheng X, Cao JG, Xiang HL, Liu F and Lv Y: 8-Bromo-7-methoxychrysin-induced apoptosis of hepatocellular carcinoma cells involves ROS and JNK. World J Gastroenterol. 16:3385–3393. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Reuter S, Eifes S, Dicato M, Aggarwal BB and Diederich M: Modulation of anti-apoptotic and survival pathways by curcumin as a strategy to induce apoptosis in cancer cells. Biochem Pharmacol. 76:1340–1351. 2008. View Article : Google Scholar : PubMed/NCBI

18 

Polier G, Ding J, Konkimalla BV, et al: Wogonin and related natural flavones are inhibitors of CDK9 that induce apoptosis in cancer cells by transcriptional suppression of Mcl-1. Cell Death Dis. 2:e1822011. View Article : Google Scholar : PubMed/NCBI

19 

Kok SH, Cheng SJ, Hong CY, et al: Norcantharidin-induced apoptosis in oral cancer cells is associated with an increase of proapoptotic to antiapoptotic protein ratio. Cancer Lett. 217:43–52. 2005. View Article : Google Scholar : PubMed/NCBI

20 

Cory S and Adams JM: The Bcl2 family: regulators of the cellular life-or-death switch. Nat Rev Cancer. 2:647–656. 2002. View Article : Google Scholar : PubMed/NCBI

21 

Brunet A, Bonni A, Zigmond MJ, et al: Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell. 96:857–868. 1999. View Article : Google Scholar : PubMed/NCBI

22 

Kops GJ, Dansen TB, Polderman PE, et al: Forkhead transcription factor FOXO3a protects quiescent cells from oxidative stress. Nature. 419:316–321. 2002. View Article : Google Scholar : PubMed/NCBI

23 

Dansen TB and Burgering BM: Unravelling the tumor-suppressive functions of FOXO proteins. Trends Cell Biol. 18:421–429. 2008. View Article : Google Scholar : PubMed/NCBI

24 

Huang H and Tindall DJ: Dynamic FoxO transcription factors. J Cell Sci. 120:2479–2487. 2007. View Article : Google Scholar : PubMed/NCBI

25 

Lee CC, Yang HL, Way TD, et al: Inhibition of cell growth and induction of apoptosis by Antrodia camphorata in HER-2/neu-overexpressing breast cancer cells through the induction of ROS, depletion of HER-2/neu, and disruption of the PI3K/Akt signaling pathway. Evid Based Complement Alternat Med. 7028572012.

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Copy and paste a formatted citation
Spandidos Publications style
Zhao X, Cao X, Liu F, Quan M, Ren K and Cao J: Regulation of the FOXO3a/Bim signaling pathway by 5,7-dihydroxy-8-nitrochrysin in MDA-MB-453 breast cancer cells. Oncol Lett 5: 929-934, 2013.
APA
Zhao, X., Cao, X., Liu, F., Quan, M., Ren, K., & Cao, J. (2013). Regulation of the FOXO3a/Bim signaling pathway by 5,7-dihydroxy-8-nitrochrysin in MDA-MB-453 breast cancer cells. Oncology Letters, 5, 929-934. https://doi.org/10.3892/ol.2012.1077
MLA
Zhao, X., Cao, X., Liu, F., Quan, M., Ren, K., Cao, J."Regulation of the FOXO3a/Bim signaling pathway by 5,7-dihydroxy-8-nitrochrysin in MDA-MB-453 breast cancer cells". Oncology Letters 5.3 (2013): 929-934.
Chicago
Zhao, X., Cao, X., Liu, F., Quan, M., Ren, K., Cao, J."Regulation of the FOXO3a/Bim signaling pathway by 5,7-dihydroxy-8-nitrochrysin in MDA-MB-453 breast cancer cells". Oncology Letters 5, no. 3 (2013): 929-934. https://doi.org/10.3892/ol.2012.1077
Copy and paste a formatted citation
x
Spandidos Publications style
Zhao X, Cao X, Liu F, Quan M, Ren K and Cao J: Regulation of the FOXO3a/Bim signaling pathway by 5,7-dihydroxy-8-nitrochrysin in MDA-MB-453 breast cancer cells. Oncol Lett 5: 929-934, 2013.
APA
Zhao, X., Cao, X., Liu, F., Quan, M., Ren, K., & Cao, J. (2013). Regulation of the FOXO3a/Bim signaling pathway by 5,7-dihydroxy-8-nitrochrysin in MDA-MB-453 breast cancer cells. Oncology Letters, 5, 929-934. https://doi.org/10.3892/ol.2012.1077
MLA
Zhao, X., Cao, X., Liu, F., Quan, M., Ren, K., Cao, J."Regulation of the FOXO3a/Bim signaling pathway by 5,7-dihydroxy-8-nitrochrysin in MDA-MB-453 breast cancer cells". Oncology Letters 5.3 (2013): 929-934.
Chicago
Zhao, X., Cao, X., Liu, F., Quan, M., Ren, K., Cao, J."Regulation of the FOXO3a/Bim signaling pathway by 5,7-dihydroxy-8-nitrochrysin in MDA-MB-453 breast cancer cells". Oncology Letters 5, no. 3 (2013): 929-934. https://doi.org/10.3892/ol.2012.1077
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