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International Journal of Molecular Medicine
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Article Open Access

Bromodomain‑containing protein 4 is critical for the antiproliferative and pro‑apoptotic effects of gambogic acid in anaplastic thyroid cancer

  • Authors:
    • Yonghui Wang
    • Wei Wang
    • Hongqin Sun
  • View Affiliations / Copyright

    Affiliations: Department of Breast Surgery, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China, Department of Breast, Thyroid and Hernia Surgery, Liaocheng People's Hospital, Liaocheng, Shandong 252000, P.R. China, Department of Central Sterile Supply, Weifang People's Hospital, Weifang, Shandong 261041, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 161-170
    |
    Published online on: April 26, 2018
       https://doi.org/10.3892/ijmm.2018.3642
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Abstract

Gambogic acid (GA) has been widely used as an anticancer drug for different tumors, including thyroid cancer. However, the potential function and molecular mechanisms of GA in anaplastic thyroid cancer (ATC) has not been illustrated thus far. The aim of the present study was to demonstrate the antitumor effects of GA on ATC cells and investigate its underlying molecular mechanisms. The results revealed that GA significantly decreased the viability and proliferation, as well as induced cell apoptosis in ATC cell lines. Next, it was demonstrated that GA decreased the expression of bromodomain‑containing protein 4 (BRD4), which has been reported to function as an oncogene in various types of cancer. BRD4 expression was significantly higher in ATC tissues compared with that in adjacent normal thyroid tissues. In addition, BRD4 silencing significantly repressed the cell viability and proliferation, and increased the cell apoptotic rate in vitro, while it also delayed the tumor growth in vivo. Notably, ectopic BRD4 expression significantly weakened the biological effects of GA on ATC cells in vitro and in vivo, which suggested that GA served its anticancer functions partially via downregulating BRD4. In conclusion, BRD4, functioning as an oncogene in ATC, is important for the antiproliferative and pro‑apoptotic effects of GA.
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View References

1 

Siegel RL, Miller KD and Jemal A: Cancer statistics, 2017. CA Cancer J Clin. 67:7–30. 2017. View Article : Google Scholar : PubMed/NCBI

2 

Nagaiah G, Hossain A, Mooney CJ, Parmentier J and Remick SC: Anaplastic thyroid cancer: A review of epidemiology, pathogenesis, and treatment. J Oncol. 2011:5423582011. View Article : Google Scholar : PubMed/NCBI

3 

O'Neill JP and Shaha AR: Anaplastic thyroid cancer. Oral Oncol. 49:702–706. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Qi Q, Lu N, Wang XT, Gu HY, Yang Y, Liu W, Li C, You QD and Guo QL: Anti-invasive effect of gambogic acid in MDA-MB-231 human breast carcinoma cells. Biochem Cell Biol. 86:386–395. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Li C, Qi Q, Lu N, Dai Q, Li F, Wang X, You Q and Guo Q: Gambogic acid promotes apoptosis and resistance to metastatic potential in MDA-MB-231 human breast carcinoma cells. Biochem Cell Biol. 90:718–730. 2012. View Article : Google Scholar : PubMed/NCBI

6 

Li D, Song XY, Yue QX, Cui YJ, Liu M, Feng LX, Wu WY, Jiang BH, Yang M, Qu XB, et al: Proteomic and bioinformatic analyses of possible target-related proteins of gambogic acid in human breast carcinoma MDA-MB-231 cells. Chin J Nat Med. 13:41–51. 2015.PubMed/NCBI

7 

Wang S, Wang L, Chen M and Wang Y: Gambogic acid sensitizes resistant breast cancer cells to doxorubicin through inhibiting P-glycoprotein and suppressing survivin expression. Chem Biol Interact. 235:76–84. 2015. View Article : Google Scholar

8 

Wang X, Deng R, Lu Y, Xu Q, Yan M, Ye D and Chen W: Gambogic acid as a non-competitive inhibitor of ATP-binding cassette transporter B1 reverses the multidrug resistance of human epithelial cancers by promoting ATP-binding cassette transporter B1 protein degradation. Basic Clin Pharmacol Toxicol. 112:25–33. 2013. View Article : Google Scholar

9 

Wang J and Yuan Z: Gambogic acid sensitizes ovarian cancer cells to doxorubicin through ROS-mediated apoptosis. Cell Biochem Biophys. 67:199–206. 2013. View Article : Google Scholar : PubMed/NCBI

10 

Zhang W, Zhou H, Yu Y, Li J, Li H, Jiang D, Chen Z, Yang D, Xu Z and Yu Z: Combination of gambogic acid with cisplatin enhances the antitumor effects on cisplatin-resistant lung cancer cells by downregulating MRP2 and LRP expression. Onco Targets Ther. 9:3359–3368. 2016. View Article : Google Scholar : PubMed/NCBI

11 

Liu WY, Wu XU, Liao CQ, Shen J and Li J: Apoptotic effect of gambogic acid in esophageal squamous cell carcinoma cells via suppression of the NF-κB pathway. Oncol Lett. 11:3681–3685. 2016. View Article : Google Scholar : PubMed/NCBI

12 

Yang Z, He N and Zhou Q: Brd4 recruits P-TEFb to chromosomes at late mitosis to promote G1 gene expression and cell cycle progression. Mol Cell Biol. 28:967–976. 2008. View Article : Google Scholar

13 

Wang YH, Sui YN, Yan K, Wang LS, Wang F and Zhou JH: BRD4 promotes pancreatic ductal adenocarcinoma cell proliferation and enhances gemcitabine resistance. Oncol Rep. 33:1699–1706. 2015. View Article : Google Scholar : PubMed/NCBI

14 

Wang YH, Sui XM, Sui YN, Zhu QW, Yan K, Wang LS, Wang F and Zhou JH: BRD4 induces cell migration and invasion in HCC cells through MMP-2 and MMP-9 activation mediated by the Sonic hedgehog signaling pathway. Oncol Lett. 10:2227–2232. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Segura MF, Fontanals-Cirera B, Gaziel-Sovran A, Guijarro MV, Hanniford D, Zhang G, González-Gomez P, Morante M, Jubierre L, Zhang W, et al: BRD4 sustains melanoma proliferation and represents a new target for epigenetic therapy. Cancer Res. 73:6264–6276. 2013. View Article : Google Scholar : PubMed/NCBI

16 

Puissant A, Frumm SM, Alexe G, Bassil CF, Qi J, Chanthery YH, Nekritz EA, Zeid R, Gustafson WC, Greninger P, et al: Targeting MYCN in neuroblastoma by BET bromodomain inhibition. Cancer Discov. 3:308–323. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Cheng Z, Gong Y, Ma Y, Lu K, Lu X, Pierce LA, Thompson RC, Muller S, Knapp S and Wang J: Inhibition of BET bromodomain targets genetically diverse glioblastoma. Clin Cancer Res. 19:1748–1759. 2013. View Article : Google Scholar : PubMed/NCBI

18 

Patel AJ, Liao CP, Chen Z, Liu C, Wang Y and Le LQ: BET bromodomain inhibition triggers apoptosis of NF1-associated malignant peripheral nerve sheath tumors through Bim induction. Cell Rep. 6:81–92. 2014. View Article : Google Scholar : PubMed/NCBI

19 

Ott CJ, Kopp N, Bird L, Paranal RM, Qi J, Bowman T, Rodig SJ, Kung AL, Bradner JE and Weinstock DM: BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia. Blood. 120:2843–2852. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Lockwood WW, Zejnullahu K, Bradner JE and Varmus H: Sensitivity of human lung adenocarcinoma cell lines to targeted inhibition of BET epigenetic signaling proteins. Proc Natl Acad Sci USA. 109:19408–19413. 2012. View Article : Google Scholar : PubMed/NCBI

21 

Andrieu G, Tran AH, Strissel KJ and Denis GV: BRD4 regulates breast cancer dissemination through Jagged1/Notch1 signaling. Cancer Res. 76:6555–6567. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Molinaro E, Romei C, Biagini A, Sabini E, Agate L, Mazzeo S, Materazzi G, Sellari-Franceschini S, Ribechini A, Torregrossa L, et al: Anaplastic thyroid carcinoma: From clinicopathology to genetics and advanced therapies. Nat Rev Endocrinol. 13:644–660. 2017. View Article : Google Scholar : PubMed/NCBI

23 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔC T method. Methods. 25:402–408. 2001. View Article : Google Scholar

24 

Gao X, Wu X, Zhang X, Hua W and Zhang Y, Maimaiti Y, Gao Z and Zhang Y: Inhibition of BRD4 suppresses tumor growth and enhances iodine uptake in thyroid cancer. Biochem Biophys Res Commun. 469:679–685. 2016. View Article : Google Scholar

25 

Mio C, Lavarone E, Conzatti K, Baldan F, Toffoletto B, Puppin C, Filetti S, Durante C, Russo D, Orlacchio A, et al: MCM5 as a target of BET inhibitors in thyroid cancer cells. Endocr Relat Cancer. 23:335–347. 2016. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Wang Y, Wang W and Sun H: Bromodomain‑containing protein 4 is critical for the antiproliferative and pro‑apoptotic effects of gambogic acid in anaplastic thyroid cancer. Int J Mol Med 42: 161-170, 2018.
APA
Wang, Y., Wang, W., & Sun, H. (2018). Bromodomain‑containing protein 4 is critical for the antiproliferative and pro‑apoptotic effects of gambogic acid in anaplastic thyroid cancer. International Journal of Molecular Medicine, 42, 161-170. https://doi.org/10.3892/ijmm.2018.3642
MLA
Wang, Y., Wang, W., Sun, H."Bromodomain‑containing protein 4 is critical for the antiproliferative and pro‑apoptotic effects of gambogic acid in anaplastic thyroid cancer". International Journal of Molecular Medicine 42.1 (2018): 161-170.
Chicago
Wang, Y., Wang, W., Sun, H."Bromodomain‑containing protein 4 is critical for the antiproliferative and pro‑apoptotic effects of gambogic acid in anaplastic thyroid cancer". International Journal of Molecular Medicine 42, no. 1 (2018): 161-170. https://doi.org/10.3892/ijmm.2018.3642
Copy and paste a formatted citation
x
Spandidos Publications style
Wang Y, Wang W and Sun H: Bromodomain‑containing protein 4 is critical for the antiproliferative and pro‑apoptotic effects of gambogic acid in anaplastic thyroid cancer. Int J Mol Med 42: 161-170, 2018.
APA
Wang, Y., Wang, W., & Sun, H. (2018). Bromodomain‑containing protein 4 is critical for the antiproliferative and pro‑apoptotic effects of gambogic acid in anaplastic thyroid cancer. International Journal of Molecular Medicine, 42, 161-170. https://doi.org/10.3892/ijmm.2018.3642
MLA
Wang, Y., Wang, W., Sun, H."Bromodomain‑containing protein 4 is critical for the antiproliferative and pro‑apoptotic effects of gambogic acid in anaplastic thyroid cancer". International Journal of Molecular Medicine 42.1 (2018): 161-170.
Chicago
Wang, Y., Wang, W., Sun, H."Bromodomain‑containing protein 4 is critical for the antiproliferative and pro‑apoptotic effects of gambogic acid in anaplastic thyroid cancer". International Journal of Molecular Medicine 42, no. 1 (2018): 161-170. https://doi.org/10.3892/ijmm.2018.3642
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