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Article Open Access

Tristetraprolin: A novel target of diallyl disulfide that inhibits the progression of breast cancer

  • Authors:
    • Ting Xiong
    • Xiao‑Wang Liu
    • Xue‑Long Huang
    • Xiong‑Feng Xu
    • Wei‑Quan Xie
    • Su‑Jun Zhang
    • Jian Tu
  • View Affiliations / Copyright

    Affiliations: Institute of Pharmacy and Pharmacology, Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study, University of South China, Hengyang, Hunan 421001, P.R. China, Experimental Animal Department, University of South China, Hengyang, Hunan 421001, P.R. China
    Copyright: © Xiong et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 7817-7827
    |
    Published online on: March 20, 2018
       https://doi.org/10.3892/ol.2018.8299
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Abstract

Diallyl disulfide (DADS), a volatile component of garlic oil, has various biological properties, including antioxidant, antiangiogenic and anticancer effects. The present study aimed to explore novel targets of DADS that may slow or stop the progression of breast cancer. First, xenograft tumor models were created by subcutaneously injecting MCF‑7 and MDA‑MB‑231 breast cancer cells into nude mice. Subsequently, western blot analysis was performed to investigate the expression of tristetraprolin (TTP), urokinase‑type plasminogen activator (uPA) and matrix metalloproteinase‑9 (MMP‑9) in the xenograft tumors, and cell cultures. Tablet cloning, Transwell and wound healing assays revealed that DADS treatment significantly inhibited the proliferation, invasion and migration of breast cancer cells. In addition, DADS treatment led to significant downregulation of uPA and MMP‑9 protein expression, but significantly upregulated TTP expression in vivo and in vitro. Knocking down TTP expression using small interfering RNA reversed the aforementioned effects of DADS, which suggests TTP is a key target of DADS in inhibiting the progression of breast cancer.
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1 

Niu HY, Niu CY, Wang JH, Zhang Y and He P: Health-related quality of life in women with breast cancer: A literature-based review of psychometric properties of breast cancer-specific measures. Asian Pac J Cancer Prev. 15:3533–3536. 2014. View Article : Google Scholar : PubMed/NCBI

2 

Lee Katie SY and Knobf MT: Primary breast cancer decision-making among Chinese American Women: Satisfaction, regret. Nurs Res. 64:391–401. 2015. View Article : Google Scholar : PubMed/NCBI

3 

Shao S and Zhao X, Zhang X, Luo M, Zuo X, Huang S, Wang Y, Gu S and Zhao X: Notch1 signaling regulates the epithelial-mesenchymal transition and invasion of breast cancer in a Slug-dependent manner. Mol Cancer. 14:282015. View Article : Google Scholar : PubMed/NCBI

4 

Xiao X, Chen B, Liu X, Liu P, Zheng G, Ye F, Tang H and Xie X: Diallyl disulfide suppresses SRC/Ras/ERK signaling-mediated proliferation and metastasis in human breast cancer by up-regulating miR-34a. PLoS One. 9:e1127202014. View Article : Google Scholar : PubMed/NCBI

5 

Su B, Su J, Zeng Y, Liu F, Xia H, Ma YH, Zhou ZG, Zhang S, Yang BM, Wu YH, et al: Diallyl disulfide suppresses epithelial-mesenchymal transition, invasion and proliferation by downregulation of LIMK1 in gastric cancer. Oncotarget. 7:10498–10512. 2016.PubMed/NCBI

6 

Lai KC, Hsu SC, Kuo CL, Yang JS, Ma CY, Lu HF, Tang NY, Hsia TC, Ho HC and Chung JG: Diallyl sulfide, diallyl disulfide, and diallyl trisulfide inhibit migration and invasion in human colon cancer colo 205 cells through the inhibition of matrix metalloproteinase-2, −7, and −9 expressions. Environ Toxicol. 28:479–488. 2013. View Article : Google Scholar : PubMed/NCBI

7 

Luo N, Zhao LC, Shi QQ, Feng ZQ, Chen DL and Li J: Induction of apoptosis in human leukemic cell lines by diallyl disulfide via modulation of EGFR/ERK/PKM2 signaling pathways. Asian Pac J Cancer Prev. 16:3509–3515. 2015. View Article : Google Scholar : PubMed/NCBI

8 

Huang J, Yang B, Xiang T, Peng W, Qiu Z, Wan J, Zhang L, Li H, Li H and Ren G: Diallyl disulfide inhibits growth and metastatic potential of human triple-negative breast cancer cells through inactivation of the β-catenin signaling pathway. Mol Nutr Food Res. 59:1063–1075. 2015. View Article : Google Scholar : PubMed/NCBI

9 

Ciocci M, Iorio E, Carotenuto F, Khashoggi HA, Nanni F and Melino S: H2S-releasing nanoemulsions: A new formulation to inhibit tumor cells proliferation and improve tissue repair. Oncotarget. 7:84338–84358. 2016. View Article : Google Scholar : PubMed/NCBI

10 

Yi L, Shan J, Chen X, Li G, Li L, Tan H and Su Q: Involvement of calreticulin in cell proliferation, invasion and differentiation in diallyl disulfide-treated HL-60 cells. Oncol Lett. 12:1861–1867. 2016. View Article : Google Scholar : PubMed/NCBI

11 

Su B, Su J, He H, Wu Y, Xia H, Zeng X, Dai W, Ai X, Ling H, Jiang H and Su Q: Identification of potential targets for diallyl disulfide in human gastric cancer MGC-803 cells using proteomics approaches. Oncol Rep. 33:2484–2494. 2015. View Article : Google Scholar : PubMed/NCBI

12 

Sun Y, Wang X, Zhou Q, Lu Y, Zhang H, Chen Q, Zhao M and Su S: Inhibitory effect of emodin on migration, invasion and metastasis of human breast cancer MDA-MB-231 cells in vitro and in vivo. Oncol Rep. 33:338–346. 2015. View Article : Google Scholar : PubMed/NCBI

13 

Jacob A and Prekeris R: The regulation of MMP targeting to invadopodia during cancer metastasis. Front Cell Dev Biol. 3:42015. View Article : Google Scholar : PubMed/NCBI

14 

Lampelj M, Arko D, Cas-Sikosek N, Kavalar R, Ravnik M, Jezersek-Novakovic B, Dobnik S, Dovnik NF and Takac I: Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) in breast cancer-correlation with traditional prognostic factors. Radiol Oncol. 49:357–364. 2015. View Article : Google Scholar : PubMed/NCBI

15 

Melanson BD, Bose R, Hamill JD, Marcellus KA, Pan EF and McKay BC: The role of mRNA decay in p53 induced gene expression. RNA. 17:2222–2234. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Brooks SA and Blackshear PJ: Tristetraprolin (TTP): Interactions with mRNA and proteins, and current thoughts on mechanisms of action. Biochim Biophys Acta. 1829:666–679. 2013. View Article : Google Scholar : PubMed/NCBI

17 

Barrios-García T, Tecalco-Cruz A, Gómez-Romero V, Reyes-Carmona S, Meneses-Morales I and León-Del-Río A: Tristetraprolin represses estrogen receptor α transactivation in breast cancer cells. J Biol Chem. 289:15554–15565. 2014. View Article : Google Scholar : PubMed/NCBI

18 

Tran DDH, Koch A, Allister A, Saran S, Ewald F, Koch M, Nashan B and Tamura T: Treatment with MAPKAP2 (MK2) inhibitor and DNA methylation inhibitor, 5-aza dC, synergistically triggers apoptosis in hepatocellular carcinoma (HCC) via tristetraprolin (TTP). Cell Signal. 28:1872–1880. 2016. View Article : Google Scholar : PubMed/NCBI

19 

Van Tubergen EA, Banerjee R, Liu M, Vander Broek R, Light E, Kuo S, Feinberg SE, Willis AL, Wolf G, Carey T, et al: Inactivation or loss of TTP promotes invasion in head and neck cancer via transcript stabilization and secretion of MMP9, MMP2, and IL-6. Clin Cancer Res. 19:1169–1179. 2013. View Article : Google Scholar : PubMed/NCBI

20 

Redig AJ and McAllister SS: Breast cancer as a systemic disease: A view of metastasis. J Intern Med. 274:113–126. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Warrier S, Tapia G, Goltsman D and Beith J: An update in breast cancer screening and management. Womens Health (Lond). 12:229–239. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Lei XY, Yao SQ, Zu XY, Huang ZX, Liu LJ, Zhong M, Zhu BY, Tang SS and Liao DF: Apoptosis induced by diallyl disulfide in human breast cancer cell line MCF-7. Acta Pharmacol Sin. 29:1233–1239. 2008. View Article : Google Scholar : PubMed/NCBI

23 

Wang G, Liu G, Ye Y, Fu Y and Zhang X: Upregulation of miR-34a by diallyl disulfide suppresses invasion and induces apoptosis in SGC-7901 cells through inhibition of the PI3K/Akt signaling pathway. Oncol Lett. 11:2661–2667. 2016. View Article : Google Scholar : PubMed/NCBI

24 

Pei S, Yang X, Wang H, Zhang H, Zhou B, Zhang D and Lin D: Plantamajoside, a potential anti-tumor herbal medicine inhibits breast cancer growth and pulmonary metastasis by decreasing the activity of matrix metalloproteinase-9 and −2. BMC Cancer. 15:9652015. View Article : Google Scholar : PubMed/NCBI

25 

Noh H, Hong S and Huang S: Role of urokinase receptor in tumor progression and development. Theranostics. 3:487–495. 2013. View Article : Google Scholar : PubMed/NCBI

26 

Page-McCaw A, Ewald AJ and Werb Z: Matrix metalloproteinases and the regulation of tissue remodelling. Nat Rev Mol Cell Biol. 8:221–233. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Moirangthem A, Bondhopadhyay B, Mukherjee M, Bandyopadhyay A, Mukherjee N, Konar K, Bhattacharya S and Basu A: Simultaneous knockdown of uPA and MMP9 can reduce breast cancer progression by increasing cell-cell adhesion and modulating EMT genes. Sci Rep. 6:219032016. View Article : Google Scholar : PubMed/NCBI

28 

Shi C, Zhang N, Feng Y, Cao J, Chen X and Liu B: Aspirin inhibits IKK-β-mediated prostate cancer cell invasion by targeting matrix Metalloproteinase-9 and Urokinase-Type plasminogen activator. Cell Physiol Biochem. 41:1313–1324. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Tong W, Wang Q, Sun D and Suo J: Curcumin suppresses colon cancer cell invasion via AMPK-induced inhibition of NF-κB, uPA activator and MMP9. Oncol Lett. 12:4139–4146. 2016. View Article : Google Scholar : PubMed/NCBI

30 

Guo J, Qu H, Chen Y and Xia J: The role of RNA-binding protein tristetraprolin in cancer and immunity. Med Oncol. 34:1962017. View Article : Google Scholar : PubMed/NCBI

31 

Griseri P, Bourcier C, Hieblot C, Essafi-Benkhadir K, Chamorey E, Touriol C and Pagès G: A synonymous polymorphism of the Tristetraprolin (TTP) gene, an AU-rich mRNA-binding protein, affects translation efficiency and response to Herceptin treatment in breast cancer patients. Hum Mol Genet. 20:4556–4568. 2011. View Article : Google Scholar : PubMed/NCBI

32 

Sobolewski C, Sanduja S, Blanco FF, Hu L and Dixon DA: Histone deacetylase inhibitors activate tristetraprolin expression through induction of early growth response protein 1 (EGR1) in colorectal cancer cells. Biomolecules. 5:2035–2055. 2015. View Article : Google Scholar : PubMed/NCBI

33 

Pandiri I, Chen Y, Joe Y, Kim HJ, Park J, Chung HT and Park JW: Tristetraprolin mediates the anti-proliferative effects of metformin in breast cancer cells. Breast Cancer Res Treat. 156:57–64. 2016. View Article : Google Scholar : PubMed/NCBI

34 

Ryu J, Yoon NA, Lee YK, Jeong JY, Kang S, Seong H, Choi J, Park N, Kim N, Cho WJ, et al: Tristetraprolin inhibits the growth of human glioma cells through downregulation of urokinase plasminogen activator/urokinase plasminogen activator receptor mRNAs. Mol Cells. 38:156–162. 2015.PubMed/NCBI

35 

Prabhala P and Ammit AJ: Tristetraprolin and its role in regulation of airway inflammation. Mol Pharmacol. 87:629–638. 2015. View Article : Google Scholar : PubMed/NCBI

36 

Gebeshuber CA, Zatloukal K and Martinez J: miR-29a suppresses tristetraprolin, which is a regulator of epithelial polarity and metastasis. EMBO Rep. 10:400–405. 2009. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Xiong T, Liu XW, Huang XL, Xu XF, Xie WQ, Zhang SJ and Tu J: Tristetraprolin: A novel target of diallyl disulfide that inhibits the progression of breast cancer. Oncol Lett 15: 7817-7827, 2018.
APA
Xiong, T., Liu, X., Huang, X., Xu, X., Xie, W., Zhang, S., & Tu, J. (2018). Tristetraprolin: A novel target of diallyl disulfide that inhibits the progression of breast cancer. Oncology Letters, 15, 7817-7827. https://doi.org/10.3892/ol.2018.8299
MLA
Xiong, T., Liu, X., Huang, X., Xu, X., Xie, W., Zhang, S., Tu, J."Tristetraprolin: A novel target of diallyl disulfide that inhibits the progression of breast cancer". Oncology Letters 15.5 (2018): 7817-7827.
Chicago
Xiong, T., Liu, X., Huang, X., Xu, X., Xie, W., Zhang, S., Tu, J."Tristetraprolin: A novel target of diallyl disulfide that inhibits the progression of breast cancer". Oncology Letters 15, no. 5 (2018): 7817-7827. https://doi.org/10.3892/ol.2018.8299
Copy and paste a formatted citation
x
Spandidos Publications style
Xiong T, Liu XW, Huang XL, Xu XF, Xie WQ, Zhang SJ and Tu J: Tristetraprolin: A novel target of diallyl disulfide that inhibits the progression of breast cancer. Oncol Lett 15: 7817-7827, 2018.
APA
Xiong, T., Liu, X., Huang, X., Xu, X., Xie, W., Zhang, S., & Tu, J. (2018). Tristetraprolin: A novel target of diallyl disulfide that inhibits the progression of breast cancer. Oncology Letters, 15, 7817-7827. https://doi.org/10.3892/ol.2018.8299
MLA
Xiong, T., Liu, X., Huang, X., Xu, X., Xie, W., Zhang, S., Tu, J."Tristetraprolin: A novel target of diallyl disulfide that inhibits the progression of breast cancer". Oncology Letters 15.5 (2018): 7817-7827.
Chicago
Xiong, T., Liu, X., Huang, X., Xu, X., Xie, W., Zhang, S., Tu, J."Tristetraprolin: A novel target of diallyl disulfide that inhibits the progression of breast cancer". Oncology Letters 15, no. 5 (2018): 7817-7827. https://doi.org/10.3892/ol.2018.8299
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