Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Experimental and Therapeutic Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-0981 Online ISSN: 1792-1015
Journal Cover
September-2021 Volume 22 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
September-2021 Volume 22 Issue 3

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article Open Access

ChaC glutathione specific γ‑glutamylcyclotransferase 1 inhibits cell viability and increases the sensitivity of prostate cancer cells to docetaxel by inducing endoplasmic reticulum stress and ferroptosis

  • Authors:
    • Saifei He
    • Miao Zhang
    • Ying Ye
    • Juhua Zhuang
    • Xing Ma
    • Yanan Song
    • Wei Xia
  • View Affiliations / Copyright

    Affiliations: Central Laboratory, The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Pudong, Shanghai 200137, P.R. China, Department of Nuclear Medicine, The Seventh People's Hospital of Shanghai University of Traditional Chinese Medicine, Pudong, Shanghai 200137, P.R. China
    Copyright: © He et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 997
    |
    Published online on: July 15, 2021
       https://doi.org/10.3892/etm.2021.10429
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The present study aimed to determine the effects and mechanism of ChaC glutathione specific γ‑glutamylcyclotransferase 1 (CHAC1) on cell viability and the sensitivity of prostate cancer cells to docetaxel. Compared with non‑tumor human prostate epithelial RWPE‑1 cells, the mRNA and protein levels of CHAC1 significantly decreased in two prostate cancer cell lines, DU145 and 22RV1, as measured by quantitative polymerase chain reaction and western blot analysis (P<0.05). The cell viability and glutathione (GSH) levels were significantly inhibited in prostate cancer cells following overexpression of CHAC1 (P<0.01), while they were significantly increased in DU145 cells transfected with CHAC1 siRNA (P<0.05), but not in 22RV1 cells (P>0.05). The expression levels of several endoplasmic reticulum (ER) stress‑related factors were then measured by western blot analysis. Following transfection with plasmid overexpressing CHAC1, ER markers, BIP and CHOP levels, were significantly upregulated (P<0.01), while GSH co‑treatment decreased this upregulation. In addition, CHAC1 protein levels were significantly upregulated in cells treated with a ferroptosis activator (P<0.05). A liperflo reagent was then used to determine intracellular lipid peroxide levels. The intracellular lipid peroxides levels were significantly increased following CHAC1‑overexpression (P<0.05), while GPX4 protein levels were significantly decreased (P<0.01). The cell viability was significantly inhibited (P<0.001) even with 1 nM docetaxel (DTX) and a plasmid overexpressing CHAC1, while the effect of inhibition was not significant at 1 nM of DTX alone (P>0.05). This inhibition was also eliminated following the addition of a ferroptosis inhibitor. In summary, CHAC1 may inhibit cell viability and increase the sensitivity of prostate cancer cells to DTX. The cellular mechanism may involve the induction of ER stress and ferroptosis. The results of the present study identified a potentially novel therapeutic target for prostate cancer, which may be useful in patients with castration‑resistant prostate cancer.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA and Jemal A: Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 68:394–424. 2018.PubMed/NCBI View Article : Google Scholar

2 

Xiao L, Tien JC, Vo J, Tan M, Parolia A, Zhang Y, Wang L, Qiao Y, Shukla S, Wang X, et al: Epigenetic reprogramming with antisense oligonucleotides enhances the effectiveness of androgen receptor inhibition in castration-resistant prostate cancer. Cancer Res. 78:5731–5740. 2018.PubMed/NCBI View Article : Google Scholar

3 

Liao Y, Guo Z, Xia X, Liu Y, Huang C, Jiang L, Wang X, Liu J and Huang H: Inhibition of EGFR signaling with Spautin-1 represents a novel therapeutics for prostate cancer. J Exp Clin Cancer Res. 38(157)2019.PubMed/NCBI View Article : Google Scholar

4 

Mungrue IN, Pagnon J, Kohannim O, Gargalovic PS and Lusis AJ: CHAC1/MGC4504 is a novel proapoptotic component of the unfolded protein response, downstream of the ATF4-ATF3-CHOP cascade. J Immunol. 82:466–476. 2009.PubMed/NCBI View Article : Google Scholar

5 

Perra L, Balloy V, Foussigniere T, Moissenet D, Petat H, Mungrue IN, Touqui L, Corvol H, Chignard M and Guillot L: CHAC1 is differentially expressed in normal and cystic fibrosis bronchial epithelial cells and regulates the inflammatory response induced by pseudomonas aeruginosa. Front Immunol. 9(2823)2018.PubMed/NCBI View Article : Google Scholar

6 

Crawford RR, Prescott ET, Sylvester CF, Higdon AN, Shan J, Kilberg MS and Mungrue IN: Human CHAC1 protein degrades glutathione, and mRNA induction is regulated by the transcription factors ATF4 and ATF3 and a bipartite ATF/CRE regulatory element. J Biol Chem. 290:15878–15891. 2015.PubMed/NCBI View Article : Google Scholar

7 

Kumar A, Tikoo S, Maity S, Sengupta S, Sengupta S, Kaur A and Bachhawat AK: Mammalian proapoptotic factor ChaC1 and its homologues function as γ-glutamyl cyclotransferases acting specifically on glutathione. EMBO Rep. 13:1095–1101. 2012.PubMed/NCBI View Article : Google Scholar

8 

Ogawa T, Wada Y, Takemura K, Board PG, Uchida K, Kitagaki K, Tamura T, Suzuki T, Tokairin Y, Nakajima Y and Eishi Y: CHAC1 overexpression in human gastric parietal cells with Helicobacter pylori infection in the secretory canaliculi. Helicobacter. 24(e12598)2019.PubMed/NCBI View Article : Google Scholar

9 

Yang WS, SriRamaratnam R, Welsch ME, Shimada K, Skouta R, Viswanathan VS, Cheah JH, Clemons PA, Shamji AF, Clish CB, et al: Regulation of ferroptotic cancer cell death by GPX4. Cell. 156:317–331. 2014.PubMed/NCBI View Article : Google Scholar

10 

Shi ZZ, Fan ZW, Chen YX, Xie XF, Jiang W, Wang WJ, Qiu YT and Bai J: Ferroptosis in carcinoma: Regulatory mechanisms and new method for cancer therapy. Onco Targets Ther. 12:11291–11304. 2019.PubMed/NCBI View Article : Google Scholar

11 

Bebber CM, Muller F, Prieto Clemente L, Weber J and von Karstedt S: Ferroptosis in cancer cell biology. Cancers (Basel). 12(164)2020.PubMed/NCBI View Article : Google Scholar

12 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001.PubMed/NCBI View Article : Google Scholar

13 

Yadav S, Chawla B, Khursheed MA, Ramachandran R and Bachhawat AK: The glutathione degrading enzyme, Chac1, is required for calcium signaling in developing zebrafish: Redox as an upstream activator of calcium. Biochem J. 476:1857–1873. 2019.PubMed/NCBI View Article : Google Scholar

14 

Chadwick SR and Lajoie P: Endoplasmic reticulum stress coping mechanisms and lifespan regulation in health and diseases. Front Cell Dev Biol. 7(84)2019.PubMed/NCBI View Article : Google Scholar

15 

Zeeshan HM, Lee GH, Kim HR and Chae HJ: Endoplasmic reticulum stress and associated ROS. Int J Mol Sci. 17(327)2016.PubMed/NCBI View Article : Google Scholar

16 

Siwecka N, Rozpedek W, Pytel D, Wawrzynkiewicz A, Dziki A, Dziki Ł, Diehl JA and Majsterek I: Dual role of endoplasmic reticulum stress-mediated unfolded protein response signaling pathway in carcinogenesis. Int J Mol Sci. 20(4354)2019.PubMed/NCBI View Article : Google Scholar

17 

Scheffer D, Kulcsár G, Nagyéri G, Kiss-Merki M, Rékási Z, Maloy M and Czömpöly T: Active mixture of serum-circulating small molecules selectively inhibits proliferation and triggers apoptosis in cancer cells via induction of ER stress. Cell Signal. 65(109426)2020.PubMed/NCBI View Article : Google Scholar

18 

Cao SS and Kaufman RJ: Endoplasmic reticulum stress and oxidative stress in cell fate decision and human disease. Antioxid Redox Signal. 21:396–413. 2014.PubMed/NCBI View Article : Google Scholar

19 

Gagliardi M, Cotella D, Santoro C, Corà D, Barlev NA, Piacentini M and Corazzari M: Aldo-keto reductases protect metastatic melanoma from ER stress-independent ferroptosis. Cell Death Dis. 10(902)2019.PubMed/NCBI View Article : Google Scholar

20 

Dixon SJ, Patel DN, Welsch M, Skouta R, Lee ED, Hayano M, Thomas AG, Gleason CE, Tatonetti NP, Slusher BS and Stockwell BR: Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis. Elife. 3(e02523)2014.PubMed/NCBI View Article : Google Scholar

21 

Lee YS, Lee DH, Choudry HA, Bartlett DL and Lee YJ: Ferroptosis-induced endoplasmic reticulum stress: Cross-talk between ferroptosis and apoptosis. Mol Cancer Res. 16:1073–1076. 2018.PubMed/NCBI View Article : Google Scholar

22 

Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, Patel DN, Bauer AJ, Cantley AM, Yang WS, et al: Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell. 149:1060–1072. 2012.PubMed/NCBI View Article : Google Scholar

23 

Cao JY and Dixon SJ: Mechanisms of ferroptosis. Cell Mol Life Sci. 73:2195–2209. 2016.PubMed/NCBI View Article : Google Scholar

24 

Chen MS, Wang SF, Hsu CY, Yin PH, Yeh TS, Lee HC and Tseng LM: CHAC1 degradation of glutathione enhances cystine-starvation-induced necroptosis and ferroptosis in human triple negative breast cancer cells via the GCN2-eIF2α-ATF4 pathway. Oncotarget. 8:114588–114602. 2017.PubMed/NCBI View Article : Google Scholar

25 

Miao L, Guo S, Lin CM, Liu Q and Huang L: Nanoformulations for combination or cascade anticancer therapy. Adv Drug Deliv Rev. 115:3–22. 2017.PubMed/NCBI View Article : Google Scholar

26 

Xiao B, Ma L and Merlin D: Nanoparticle-mediated co-delivery of chemotherapeutic agent and siRNA for combination cancer therapy. Expert Opin Drug Deliv. 14:65–73. 2017.PubMed/NCBI View Article : Google Scholar

27 

Chen CK, Law WC, Aalinkeel R, Yu Y, Nair B, Wu J, Mahajan S, Reynolds JL, Li Y, Lai CK, et al: Biodegradable cationic polymeric nanocapsules for overcoming multidrug resistance and enabling drug-gene co-delivery to cancer cells. Nanoscale. 6:1567–1572. 2014.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
He S, Zhang M, Ye Y, Zhuang J, Ma X, Song Y and Xia W: ChaC glutathione specific γ‑glutamylcyclotransferase 1 inhibits cell viability and increases the sensitivity of prostate cancer cells to docetaxel by inducing endoplasmic reticulum stress and ferroptosis. Exp Ther Med 22: 997, 2021.
APA
He, S., Zhang, M., Ye, Y., Zhuang, J., Ma, X., Song, Y., & Xia, W. (2021). ChaC glutathione specific γ‑glutamylcyclotransferase 1 inhibits cell viability and increases the sensitivity of prostate cancer cells to docetaxel by inducing endoplasmic reticulum stress and ferroptosis. Experimental and Therapeutic Medicine, 22, 997. https://doi.org/10.3892/etm.2021.10429
MLA
He, S., Zhang, M., Ye, Y., Zhuang, J., Ma, X., Song, Y., Xia, W."ChaC glutathione specific γ‑glutamylcyclotransferase 1 inhibits cell viability and increases the sensitivity of prostate cancer cells to docetaxel by inducing endoplasmic reticulum stress and ferroptosis". Experimental and Therapeutic Medicine 22.3 (2021): 997.
Chicago
He, S., Zhang, M., Ye, Y., Zhuang, J., Ma, X., Song, Y., Xia, W."ChaC glutathione specific γ‑glutamylcyclotransferase 1 inhibits cell viability and increases the sensitivity of prostate cancer cells to docetaxel by inducing endoplasmic reticulum stress and ferroptosis". Experimental and Therapeutic Medicine 22, no. 3 (2021): 997. https://doi.org/10.3892/etm.2021.10429
Copy and paste a formatted citation
x
Spandidos Publications style
He S, Zhang M, Ye Y, Zhuang J, Ma X, Song Y and Xia W: ChaC glutathione specific γ‑glutamylcyclotransferase 1 inhibits cell viability and increases the sensitivity of prostate cancer cells to docetaxel by inducing endoplasmic reticulum stress and ferroptosis. Exp Ther Med 22: 997, 2021.
APA
He, S., Zhang, M., Ye, Y., Zhuang, J., Ma, X., Song, Y., & Xia, W. (2021). ChaC glutathione specific γ‑glutamylcyclotransferase 1 inhibits cell viability and increases the sensitivity of prostate cancer cells to docetaxel by inducing endoplasmic reticulum stress and ferroptosis. Experimental and Therapeutic Medicine, 22, 997. https://doi.org/10.3892/etm.2021.10429
MLA
He, S., Zhang, M., Ye, Y., Zhuang, J., Ma, X., Song, Y., Xia, W."ChaC glutathione specific γ‑glutamylcyclotransferase 1 inhibits cell viability and increases the sensitivity of prostate cancer cells to docetaxel by inducing endoplasmic reticulum stress and ferroptosis". Experimental and Therapeutic Medicine 22.3 (2021): 997.
Chicago
He, S., Zhang, M., Ye, Y., Zhuang, J., Ma, X., Song, Y., Xia, W."ChaC glutathione specific γ‑glutamylcyclotransferase 1 inhibits cell viability and increases the sensitivity of prostate cancer cells to docetaxel by inducing endoplasmic reticulum stress and ferroptosis". Experimental and Therapeutic Medicine 22, no. 3 (2021): 997. https://doi.org/10.3892/etm.2021.10429
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team