Open Access

Tunicamycin suppresses breast cancer cell growth and metastasis via regulation of the protein kinase B/nuclear factor-κB signaling pathway

  • Authors:
    • Xiaoli Wang
    • Wei Xiong
    • Yiyin Tang
  • View Affiliations

  • Published online on: January 26, 2018     https://doi.org/10.3892/ol.2018.7874
  • Pages: 4137-4142
  • Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Breast cancer is one of the most common metastatic tumor types. Reports have suggested that Tunicamycin may inhibit the aggressiveness of cancer cells by promoting their apoptosis. In the present study, the inhibitory effects of Tunicamycin were investigated and the potential molecular mechanism underlying the Tunicamycin‑inhibited growth and aggressiveness of breast cancer cells was explored. In vitro assays demonstrated that Tunicamycin significantly inhibited growth and arrested the cell cycle of breast cancer cells in a dose‑dependent manner, compared with control cells. Results revealed that Tunicamycin treatment suppressed the migration and invasion of breast cancer cells. Significantly increased apoptosis of breast cancer cells was observed subsequent to Tunicamycin treatment, as compared with control cells. Mechanism analysis demonstrated that Tunicamycin inhibited the protein kinase B (Akt) and nuclear factor‑κB (NF‑κB) signaling pathways, whilst Akt overexpression significantly cancelled out the Tunicamycin‑inhibited growth and aggressiveness of breast cancer cells, as compared with control cells. In vivo assays revealed that Tunicamycin treatment significantly inhibited tumor growth and significantly prolonged the survival of tumor‑bearing mice, compared with the PBS‑treated group. In conclusion, these results indicate that Tunicamycin may inhibit the growth and aggressiveness of breast cancer cells via regulation of the Akt/NF-κB signaling pathway.

References

1 

Benson R, Madan R, Julka PK and Rath GK: Metaplastic carcinoma of breast: A case series of seven patients from a tertiary care center and review of literature. Gulf J Oncolog. 1:74–76. 2016.PubMed/NCBI

2 

Conlon N, Sadri N, Corben AD and Tan LK: Acinic cell carcinoma of breast: Morphologic and immunohistochemical review of a rare breast cancer subtype. Hum Pathol. 51:16–24. 2016. View Article : Google Scholar : PubMed/NCBI

3 

Conlon N, Howard J, Catalano J, Gallagher M, Tan LK and Corben AD: Breast carcinoma in young women: No evidence of increasing rates of metastatic breast carcinoma in a single tertiary center review. Breast J. 22:287–292. 2016. View Article : Google Scholar : PubMed/NCBI

4 

Wang L, Shi JF, Huang HY, Zhu J, Li J, Fang Y and Dai M: Economic evaluation on breast cancer screening in mainland China: A systematic review. Zhonghua Liu Xing Bing Xue Za Zhi. 37:1662–1669. 2016.(In Chinese). PubMed/NCBI

5 

Banys-Paluchowski M, Krawczyk N and Fehm T: Potential role of circulating tumor cell detection and monitoring in breast cancer: A review of current evidence. Front Oncol. 6:2552016. View Article : Google Scholar : PubMed/NCBI

6 

Wei JL, Buza J III and Liu CJ: Does progranulin account for the opposite effects of etanercept and infliximab/adalimumab in osteoarthritis?: Comment on Olson et al: ‘Therapeutic opportunities to prevent post-traumatic arthritis: Lessons from the natural history of arthritis after articular fracture’. J Orthop Res. 34:12–14. 2016. View Article : Google Scholar : PubMed/NCBI

7 

Jiang CC, Chen LH, Gillespie S, Kiejda KA, Mhaidat N, Wang YF, Thorne R, Zhang XD and Hersey P: Tunicamycin sensitizes human melanoma cells to tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis by up-regulation of TRAIL-R2 via the unfolded protein response. Cancer Res. 67:5880–5888. 2007. View Article : Google Scholar : PubMed/NCBI

8 

Shiraishi T, Yoshida T, Nakata S, Horinaka M, Wakada M, Mizutani Y, Miki T and Sakai T: Tunicamycin enhances tumor necrosis factor-related apoptosis-inducing ligand-induced apoptosis in human prostate cancer cells. Cancer Res. 65:6364–6370. 2005. View Article : Google Scholar : PubMed/NCBI

9 

Delom F, Emadali A, Cocolakis E, Lebrun JJ, Nantel A and Chevet E: Calnexin-dependent regulation of tunicamycin-induced apoptosis in breast carcinoma MCF-7 cells. Cell Death Differ. 14:586–596. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Takahashi N, Iwahori A, Breitman TR and Fukui T: Tunicamycin in combination with retinoic acid synergistically inhibits cell growth while decreasing palmitoylation and enhancing retinoylation of proteins in the human breast cancer cell line MCF-7. Oncol Res. 9:527–533. 1997.PubMed/NCBI

11 

Hasegawa A, Osuga Y, Hirota Y, Hamasaki K, Kodama A, Harada M, Tajima T, Takemura Y, Hirata T, Yoshino O, et al: Tunicamycin enhances the apoptosis induced by tumor necrosis factor-related apoptosis-inducing ligand in endometriotic stromal cells. Hum Reprod. 24:408–414. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Banerjee A, Lang JY, Hung MC, Sengupta K, Banerjee SK, Baksi K and Banerjee DK: Unfolded protein response is required in nu/nu mice microvasculature for treating breast tumor with tunicamycin. J Biol Chem. 286:29127–29138. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Giordano E, Davalos A, Nicod N and Visioli F: Hydroxytyrosol attenuates tunicamycin-induced endoplasmic reticulum stress in human hepatocarcinoma cells. Mol Nutr Food Res. 58:954–962. 2014. View Article : Google Scholar : PubMed/NCBI

14 

Carlisle RE, Brimble E, Werner KE, Cruz GL, Ask K, Ingram AJ and Dickhout JG: 4-Phenylbutyrate inhibits tunicamycin-induced acute kidney injury via CHOP/GADD153 repression. PLoS One. 9:e846632014. View Article : Google Scholar : PubMed/NCBI

15 

Davey G and Wu Z: Attitudes in China toward the use of animals in laboratory research. Altern Lab Anim. 35:313–316. 2007.PubMed/NCBI

16 

Bai FL, Yu YH, Tian H, Ren GP, Wang H, Zhou B, Han XH, Yu QZ and Li DS: Genetically engineered Newcastle disease virus expressing interleukin-2 and TNF-related apoptosis-inducing ligand for cancer therapy. Cancer Biol Ther. 15:1226–1238. 2014. View Article : Google Scholar : PubMed/NCBI

17 

Li L, Yuan L, Chen X, Wang Q, Tian J, Yang K and Zhou E: Current treatments for breast cancer-related lymphoedema: A systematic review. Asian Pac J Cancer Prev. 17:4875–4883. 2016.PubMed/NCBI

18 

Han X, Zhang X, Li H, Huang S, Zhang S, Wang F and Shi Y: Tunicamycin enhances the antitumor activity of trastuzumab on breast cancer in vitro and in vivo. Oncotarget. 6:38912–38925. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Zhang Y, Liao S, Fan W, Wei W, Wang C and Sun S: Tunicamycin-induced ER stress regulates chemokine CCL5 expression and secretion via STAT3 followed by decreased transmigration of MCF-7 breast cancer cells. Oncol Rep. 32:2769–2776. 2014. View Article : Google Scholar : PubMed/NCBI

20 

Kim SH, Shin HY, Kim YS, Kang JG, Kim CS, Ihm SH, Choi MG, Yoo HJ and Lee SJ: Tunicamycin induces paraptosis potentiated by inhibition of BRAFV600E in FRO anaplastic thyroid carcinoma cells. Anticancer Res. 34:4857–4868. 2014.PubMed/NCBI

21 

Nami B, Donmez H and Kocak N: Tunicamycin-induced endoplasmic reticulum stress reduces in vitro subpopulation and invasion of CD44+/CD24-phenotype breast cancer stem cells. Exp Toxicol Pathol. 68:419–426. 2016. View Article : Google Scholar : PubMed/NCBI

22 

Andreeva VA, Unger JB and Pentz MA: Breast cancer among immigrants: A systematic review and new research directions. J Immigr Minor Health. 9:307–322. 2007. View Article : Google Scholar : PubMed/NCBI

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April 2018
Volume 15 Issue 4

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Copy and paste a formatted citation
APA
Wang, X., Xiong, W., & Tang, Y. (2018). Tunicamycin suppresses breast cancer cell growth and metastasis via regulation of the protein kinase B/nuclear factor-κB signaling pathway. Oncology Letters, 15, 4137-4142. https://doi.org/10.3892/ol.2018.7874
MLA
Wang, X., Xiong, W., Tang, Y."Tunicamycin suppresses breast cancer cell growth and metastasis via regulation of the protein kinase B/nuclear factor-κB signaling pathway". Oncology Letters 15.4 (2018): 4137-4142.
Chicago
Wang, X., Xiong, W., Tang, Y."Tunicamycin suppresses breast cancer cell growth and metastasis via regulation of the protein kinase B/nuclear factor-κB signaling pathway". Oncology Letters 15, no. 4 (2018): 4137-4142. https://doi.org/10.3892/ol.2018.7874