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
November-2022 Volume 24 Issue 5

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
November-2022 Volume 24 Issue 5

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

Thymoquinone‑induced autophagy mitigates doxorubicin‑induced H9c2 cell apoptosis

  • Authors:
    • Dawei Liu
    • Lei Zhao
  • View Affiliations / Copyright

    Affiliations: Department of Cardiovascular Surgery, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shanxi 710032, P.R. China, Department of Nephropathy, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shanxi 710032, P.R. China
  • Article Number: 694
    |
    Published online on: September 28, 2022
       https://doi.org/10.3892/etm.2022.11630
  • 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

Doxorubicin (Dox)‑induced myocardiopathy is a massive obstacle in administering chemotherapeutic drugs in cancer patients. In the present study, the effects of thymoquinone (TQ) on Dox‑induced cardiotoxicity were investigated in vitro. H9c2 cardiomyocytes were pre‑treated with TQ followed by Dox, and cell viability and cell death were subsequently measured. Flow cytometry was conducted to evaluate the apoptosis of H9c2 cells. Autophagy was assessed by immunofluorescence LC3 staining. Western blot analysis was performed to determine autophagy‑, apoptosis‑ and LKB1/AMPK‑related proteins. Dox‑induced H9c2 cell death and apoptosis were decreased after pretreatment with TQ in vitro. The number of autophagosomes and autophagic markers was further increased by TQ in the Dox‑treated H9c2 cells, which mediated LKB1/AMPK activation and the deactivation of mTOR. Suppression of autophagosomes abolished the TQ‑induced antiapoptotic effect. In conclusion, TQ reduces Dox‑induced apoptosis of cardiomyocytes by upregulating autophagy through activation of the LKB1/AMPK pathways. These novel results highlight the therapeutic potential of TQ to prevent Dox cardiotoxicity.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Gotwals P, Cameron S, Cipolletta D, Cremasco V, Crystal A, Hewes B, Mueller B, Quaratino S, Sabatos-Peyton C, Petruzzelli L, et al: Prospects for combining targeted and conventional cancer therapy with immunotherapy. Nat Rev Cancer. 17:286–301. 2017.PubMed/NCBI View Article : Google Scholar

2 

Tan TC, Neilan TG, Francis S, Plana JC and Scherrer-Crosbie M: Anthracycline-induced cardiomyopathy in adults. Compr Physiol. 5:1517–1540. 2015.PubMed/NCBI View Article : Google Scholar

3 

Octavia Y, Tocchetti CG, Gabrielson KL, Janssens S, Crijns HJ and Moens AL: Doxorubicin-induced cardiomyopathy: From molecular mechanisms to therapeutic strategies. J Mol Cell Cardiol. 52:1213–1225. 2012.PubMed/NCBI View Article : Google Scholar

4 

Zhang S, Liu X, Bawa-Khalfe T, Lu LS, Lyu YL, Liu LF and Yeh ET: Identification of the molecular basis of doxorubicin-induced cardiotoxicity. Nat Med. 18:1639–1642. 2012.PubMed/NCBI View Article : Google Scholar

5 

Li DL, Wang ZV, Ding G, Tan W, Luo X, Criollo A, Xie M, Jiang N, May H, Kyrychenko V, et al: Doxorubicin blocks cardiomyocyte autophagic flux by inhibiting lysosome acidification. Circulation. 133:1668–1687. 2016.PubMed/NCBI View Article : Google Scholar

6 

Ali BH and Blunden G: Pharmacological and toxicological properties of Nigella sativa. Phytother Res. 17:299–305. 2003.PubMed/NCBI View Article : Google Scholar

7 

Shaterzadeh-Yazdi H, Noorbakhsh MF, Hayati F, Samarghandian S and Farkhondeh T: Immunomodulatory and anti-inflammatory effects of thymoquinone. Cardiovasc Hematol Disord Drug Targets. 18:52–60. 2018.PubMed/NCBI View Article : Google Scholar

8 

Nagi MN and Mansour MA: Protective effect of thymoquinone against doxorubicin-induced cardiotoxicity in rats: A possible mechanism of protection. Pharmacol Res. 41:283–289. 2000.PubMed/NCBI View Article : Google Scholar

9 

Karabulut D, Ozturk E, Kaymak E, Akin AT and Yakan B: Thymoquinone attenuates doxorubicin-cardiotoxicity in rats. J Biochem Mol Toxicol. 35(e22618)2021.PubMed/NCBI View Article : Google Scholar

10 

Pehlivan DY, Durdagi G, Oyar EO, Akyol S and Ozbek M: The effects of melatonin and thymoquinone on doxorubicin-induced cardiotoxicity in rats. Bratisl Lek Listy. 121:753–759. 2020.PubMed/NCBI View Article : Google Scholar

11 

Curigliano G, Cardinale D, Suter T, Plataniotis G, de Azambuja E, Sandri MT, Criscitiello C, Goldhirsch A, Cipolla C and Roila F: ESMO Guidelines Working Group. Cardiovascular toxicity induced by chemotherapy, targeted agents and radiotherapy: ESMO clinical practice guidelines. Ann Oncol. 23 (Suppl 7):vii155–166. 2012.PubMed/NCBI View Article : Google Scholar

12 

Robertson ID, Naprasnik A and Morrow D: The sources of pesticide contamination in Queensland livestock. Aust Vet J. 67:152–153. 1990.PubMed/NCBI View Article : Google Scholar

13 

Wenningmann N, Knapp M, Ande A, Vaidya TR and Ait-Oudhia S: Insights into doxorubicin-induced cardiotoxicity: Molecular mechanisms, preventive strategies, and early monitoring. Mol Pharmacol. 96:219–232. 2019.PubMed/NCBI View Article : Google Scholar

14 

Al-Malky HS, Al Harthi SE and Osman AM: Major obstacles to doxorubicin therapy: Cardiotoxicity and drug resistance. J Oncol Pharm Pract. 26:434–444. 2020.PubMed/NCBI View Article : Google Scholar

15 

Ali MY, Akter Z, Mei Z, Zheng M, Tania M and Khan MA: Thymoquinone in autoimmune diseases: Therapeutic potential and molecular mechanisms. Biomed Pharmacother. 134(111157)2021.PubMed/NCBI View Article : Google Scholar

16 

Gholamnezhad Z, Havakhah S and Boskabady MH: Preclinical and clinical effects of Nigella sativa and its constituent, thymoquinone: A review. J Ethnopharmacol. 190:372–386. 2016.PubMed/NCBI View Article : Google Scholar

17 

Imran M, Rauf A, Khan IA, Shahbaz M, Qaisrani TB, Fatmawati S, Abu-Izneid T, Imran A, Rahman KU and Gondal TA: Thymoquinone: A novel strategy to combat cancer: A review. Biomed Pharmacother. 106:390–402. 2018.PubMed/NCBI View Article : Google Scholar

18 

Isaev NK, Chetverikov NS, Stelmashook EV, Genrikhs EE, Khaspekov LG and Illarioshkin SN: Thymoquinone as a potential neuroprotector in acute and chronic forms of cerebral pathology. Biochemistry (Mosc). 85:167–176. 2020.PubMed/NCBI View Article : Google Scholar

19 

Abdel-Daim MM, Abo El-Ela FI, Alshahrani FK, Bin-Jumah M, Al-Zharani M, Almutairi B, Alyousif MS, Bungau S, Aleya L and Alkahtani S: Protective effects of thymoquinone against acrylamide-induced liver, kidney and brain oxidative damage in rats. Environ Sci Pollut Res Int. 27:37709–37717. 2020.PubMed/NCBI View Article : Google Scholar

20 

Nili-Ahmadabadi A, Alibolandi P, Ranjbar A, Mousavi L, Nili-Ahmadabadi H, Larki-Harchegani A, Ahmadimoghaddam D and Omidifar N: Thymoquinone attenuates hepatotoxicity and oxidative damage caused by diazinon: An in vivo study. Res Pharm Sci. 13:500–508. 2018.PubMed/NCBI View Article : Google Scholar

21 

Alam MF, Khan G, Safhi MM, Alshahrani S, Siddiqui R, Sivagurunathan Moni S and Anwer T: Thymoquinone ameliorates doxorubicin-induced cardiotoxicity in swiss albino mice by modulating oxidative damage and cellular inflammation. Cardiol Res Pract. 2018(1483041)2018.PubMed/NCBI View Article : Google Scholar

22 

Öztürk E, Kaymak E, Akin A, Karabulut D, Ünsal HM and Yakan B: Thymoquinone is a protective agent that reduces the negative effects of doxorubicin in rat testis. Hum Exp Toxicol. 39:1364–1373. 2020.PubMed/NCBI View Article : Google Scholar

23 

Timm KN and Tyler DJ: The role of AMPK activation for cardioprotection in doxorubicin-induced cardiotoxicity. Cardiovasc Drugs Ther. 34:255–269. 2020.PubMed/NCBI View Article : Google Scholar

24 

Dirks-Naylor AJ: The role of autophagy in doxorubicin-induced cardiotoxicity. Life Sci. 93:913–916. 2013.PubMed/NCBI

25 

Shabalala S, Muller CJF, Louw J and Johnson R: Polyphenols, autophagy and doxorubicin-induced cardiotoxicity. Life Sci. 180:160–170. 2017.PubMed/NCBI View Article : Google Scholar

26 

Ma Y, Yang L, Ma J, Lu L, Wang X, Ren J and Yang J: Rutin attenuates doxorubicin-induced cardiotoxicity via regulating autophagy and apoptosis. Biochim Biophys Acta Mol Basis Dis. 1863:1904–1911. 2017.PubMed/NCBI View Article : Google Scholar

27 

Xu ZM, Li CB, Liu QL, Li P and Yang H: Ginsenoside Rg1 prevents doxorubicin-induced cardiotoxicity through the inhibition of autophagy and endoplasmic reticulum stress in mice. Int J Mol Sci. 19(3658)2018.PubMed/NCBI View Article : Google Scholar

28 

Codogno P, Mehrpour M and Proikas-Cezanne T: Canonical and non-canonical autophagy: Variations on a common theme of self-eating? Nat Rev Mol Cell Biol. 13:7–12. 2011.PubMed/NCBI View Article : Google Scholar

29 

Khan N and Sultana S: Inhibition of two stage renal carcinogenesis, oxidative damage and hyperproliferative response by Nigella sativa. Eur J Cancer Prev. 14:159–168. 2005.PubMed/NCBI View Article : Google Scholar

30 

Vance SH, Benghuzzi H, Wilson-Simpson F and Tucci M: Thymoquinone supplementation and its effect on kidney tubule epithelial cells in vitro. Biomed Sci Instrum. 44:477–482. 2008.PubMed/NCBI

31 

Mu GG, Zhang LL, Li HY, Liao Y and Yu HG: Thymoquinone pretreatment overcomes the insensitivity and potentiates the antitumor effect of gemcitabine through abrogation of notch1, PI3K/Akt/mTOR regulated signaling pathways in pancreatic cancer. Dig Dis Sci. 60:1067–1080. 2015.PubMed/NCBI View Article : Google Scholar

32 

Qadri SM, Mahmud H, Föller M and Lang F: Thymoquinone-induced suicidal erythrocyte death. Food Chem Toxicol. 47:1545–1549. 2009.PubMed/NCBI View Article : Google Scholar

33 

Khader M, Bresgen N and Eckl P: In vitro toxicological properties of thymoquinone. Food Chem Toxicol. 47:129–133. 2009.PubMed/NCBI View Article : Google Scholar

34 

Dollah MA, Parhizkar S, Latiff LA and Bin Hassan MH: Toxicity effect of Nigella sativa on the liver function of rats. Adv Pharm Bull. 3:97–102. 2013.PubMed/NCBI View Article : Google Scholar

35 

Abukhader M: The effect of route of administration in thymoquinone toxicity in male and female rats. Indian J Pharm Sci. 74(195)2012.PubMed/NCBI View Article : Google Scholar

36 

Gali-Muhtasib H, Kuester D, Mawrin C, Bajbouj K, Diestel A, Ocker M, Habold C, Foltzer-Jourdainne C, Schoenfeld P, Peters B, et al: Thymoquinone triggers inactivation of the stress response pathway sensor CHEK1 and contributes to apoptosis in colorectal cancer cells. Cancer Res. 68:5609–5618. 2008.PubMed/NCBI View Article : Google Scholar

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Liu D and Zhao L: Thymoquinone‑induced autophagy mitigates doxorubicin‑induced H9c2 cell apoptosis. Exp Ther Med 24: 694, 2022.
APA
Liu, D., & Zhao, L. (2022). Thymoquinone‑induced autophagy mitigates doxorubicin‑induced H9c2 cell apoptosis. Experimental and Therapeutic Medicine, 24, 694. https://doi.org/10.3892/etm.2022.11630
MLA
Liu, D., Zhao, L."Thymoquinone‑induced autophagy mitigates doxorubicin‑induced H9c2 cell apoptosis". Experimental and Therapeutic Medicine 24.5 (2022): 694.
Chicago
Liu, D., Zhao, L."Thymoquinone‑induced autophagy mitigates doxorubicin‑induced H9c2 cell apoptosis". Experimental and Therapeutic Medicine 24, no. 5 (2022): 694. https://doi.org/10.3892/etm.2022.11630
Copy and paste a formatted citation
x
Spandidos Publications style
Liu D and Zhao L: Thymoquinone‑induced autophagy mitigates doxorubicin‑induced H9c2 cell apoptosis. Exp Ther Med 24: 694, 2022.
APA
Liu, D., & Zhao, L. (2022). Thymoquinone‑induced autophagy mitigates doxorubicin‑induced H9c2 cell apoptosis. Experimental and Therapeutic Medicine, 24, 694. https://doi.org/10.3892/etm.2022.11630
MLA
Liu, D., Zhao, L."Thymoquinone‑induced autophagy mitigates doxorubicin‑induced H9c2 cell apoptosis". Experimental and Therapeutic Medicine 24.5 (2022): 694.
Chicago
Liu, D., Zhao, L."Thymoquinone‑induced autophagy mitigates doxorubicin‑induced H9c2 cell apoptosis". Experimental and Therapeutic Medicine 24, no. 5 (2022): 694. https://doi.org/10.3892/etm.2022.11630
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