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
Oncology Letters
Join Editorial Board Propose a Special Issue
Print ISSN: 1792-1074 Online ISSN: 1792-1082
Journal Cover
October-2018 Volume 16 Issue 4

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
October-2018 Volume 16 Issue 4

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

Piperidine nitroxide Tempol enhances cisplatin‑induced apoptosis in ovarian cancer cells

  • Authors:
    • Meng Wang
    • Keyi Li
    • Zhiwei Zou
    • Linlin Li
    • Lingqun Zhu
    • Qianli Wang
    • Wenwen Gao
    • Ying Wang
    • Wenhua Huang
    • Ruiyuan Liu
    • Kaitai Yao
    • Qiuzhen Liu
  • View Affiliations / Copyright

    Affiliations: Cancer Research Institute, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Department of Anatomy, School of Basic Medical Science, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China, Science Department of Chemistry, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China
    Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 4847-4854
    |
    Published online on: August 10, 2018
       https://doi.org/10.3892/ol.2018.9289
  • 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

A nitroxide radical, Tempol (Tempol, TPL), is usually used as an antioxidative agent clinically, whereas the mechanism underlying its pro‑oxidative effect has not been thoroughly investigated. The present study investigated the pro‑oxidative effect of TPL on the inhibition of cellular proliferation and its role in enhancing the effect of anticancer drug cisplatin (DDP) on the induction of apoptosis in ovarian cancer cells. Cell viability and proliferation were evaluated by MTT assay. Cell apoptosis was analyzed by flow cytometry (FCM) following staining with Annexin V/propidium iodide. Western blot analysis was performed to determine the expression levels of anti‑apoptotic protein B‑cell lymphoma‑2 (Bcl‑2) and pro‑apoptotic protein Bcl‑2‑associated X protein (Bax), and the Bcl‑2:Bax expression ratio. Cellular reactive oxygen species (ROS) were labeled with dichlorofluorescin‑diacetate and analyzed by FCM. The results revealed that cell viabilities of OVCAR3 and SKOV3 cells were decreased by TPL in dose‑dependent manner at concentrations of 2 to 10 mM after 48 h incubation. The cell proliferation rates of OVCAR3 and SKOV3 cells were suppressed by TPL at lower toxic concentrations of 1.5 and 1 mM, respectively, compared with the control group. The MTT assay indicated that the combination therapy significantly inhibited the cell proliferation of OVCAR3 cells compared with treatment with DDP alone. FCM demonstrated that the combination treatment increased the proportion of early apoptotic cells in OVCAR3 cells compared with single DDP treatment. Western blot analysis revealed that the combination treatment markedly decreased the Bcl‑2:Bax expression ratio compared with treatment with DDP alone. Detection of cellular ROS expression levels demonstrated that the combination therapy significantly increased cellular ROS generation compared with the DDP‑only therapy. These data indicated that TPL increased the effect of DDP on inducing apoptosis in OVCAR3 cells.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

View References

1 

Salehi F, Dunfield L, Phillips KP, Krewski D and Vanderhyden BC: Risk factors for ovarian cancer: An overview with emphas is on hormonal factors. J Toxicol Environ Health B Crit Rev. 11:301–321. 2008. View Article : Google Scholar : PubMed/NCBI

2 

Markman M: Pharmaceutical management of ovarian cancer: Current status. Drugs. 68:771–789. 2008. View Article : Google Scholar : PubMed/NCBI

3 

Mckeage MJ: Comparative adverse effect profiles of platinum drugs. Drug Saf. 13:228–244. 1995. View Article : Google Scholar : PubMed/NCBI

4 

Aisner J, Jacobs M, Sinabaldi V, Gray W and Eisenberger M: Chemoradiotherapy for the treatment of regionally advanced head and neck cancers. Semin Oncol. 21 5 Suppl 12:S35–S44. 1994.

5 

Ali BH and Al Moundhri MS: Agents ameliorating or augmenting the nephrotoxicity of cisplatin and other platinum compounds: A review of some recent research. Food Chem Toxicol. 44:1173–1183. 2006. View Article : Google Scholar : PubMed/NCBI

6 

Santos NA, Catao CS, Martins NM, Curti C, Bianchi ML and Santos AC: Cisplatin-induced nephrotoxicity is associated with oxidative stress, redox state unbalance, impairment of energetic metabolism and apoptosis in rat kidney mitochondria. Arch Toxicol. 81:495–504. 2007. View Article : Google Scholar : PubMed/NCBI

7 

Cairns RA, Harris IS and Mak TW: Regulation of cancer cell metabolism. Nat Rev Cancer. 11:85–95. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Kawanishi S, Hiraku Y, Pinlaor S and Ma N: Oxidative and nitrative DNA damage in animals and patients with inflammatory diseases in relation to inflammation-related carcinogenesis. Biol Chem. 387:365–372. 2006. View Article : Google Scholar : PubMed/NCBI

9 

Janssen-Heininger YM, Mossman BT, Heintz NH, Forman HJ, Kalyanaraman B, Finkel T, Stamler JS, Rhee SG and van der Vliet A: Redox-based regulation of signal transduction: principles, pitfalls, and promises. Free Radic Biol Med. 45:1–17. 2008. View Article : Google Scholar : PubMed/NCBI

10 

Ames BN, Shigenaga MK and Hagen TM: Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci USA. 90:7915–7922. 1993. View Article : Google Scholar : PubMed/NCBI

11 

Schafer ZT, Grassian AR, Song L, Jiang Z, Gerhart-Hines Z, Irie HY, Gao S, Puigserver P and Brugge JS: Antioxidant and oncogene rescue of metabolic defects caused by loss of matrix attachment. Nature. 461:109–113. 2009. View Article : Google Scholar : PubMed/NCBI

12 

Perry G, Raina AK, Nunomura A, Wataya T, Sayre LM and Smith MA: How important is oxidative damage? Lessons from Alzheimer's disease. Free Radic Biol Med. 28:831–834. 2000. View Article : Google Scholar : PubMed/NCBI

13 

Moloney JN and Cotter TG: ROS signalling in the biology of cancer. Semin Cell Dev Biol. 80:50–64. 2018. View Article : Google Scholar : PubMed/NCBI

14 

Brasch RC, London DA, Wesbey GE, Tozer TN, Nitecki DE, Williams RD, Doemeny J, Tuck LD and Lallemand DP: Work in progress: Nuclear magnetic resonance study of a paramagnetic nitroxide contrast agent for enhancement of renal structures in experimental animals. Radiology. 147:773–779. 1983. View Article : Google Scholar : PubMed/NCBI

15 

Tabaczar S, Talar M and Gwoździński K: Nitroxides as antioxidants-possibilities of their application in chemoprevention and radioprotection. Postepy Hig Med Dosw (Online). 65:46–54. 2011.(In Polish). View Article : Google Scholar : PubMed/NCBI

16 

Saito K, Takeshita K, Ueda J and Ozawa T: Two reaction sites of a spin label, TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl), with hydroxyl radical. J Pharm Sci. 92:275–280. 2003. View Article : Google Scholar : PubMed/NCBI

17 

Krishna MC, Grahame DA, Samuni A, Mitchell JB and Russo A: Oxoammonium cation intermediate in the nitroxide-catalyzed dismutation of superoxide. Proc Natl Acad Sci USA. 89:5537–5541. 1992. View Article : Google Scholar : PubMed/NCBI

18 

Wilcox CS and Pearlman A: Chemistry and antihypertensive effects of tempol and other nitroxides. Pharmacol Rev. 60:418–469. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Volk T, Hensel M, Schuster H and Kox WJ: Secretion of MCP-1 and IL-6 by cytokine stimulated production of reactive oxygen species in endothelial cells. Mol Cell Biochem. 206:105–112. 2000. View Article : Google Scholar : PubMed/NCBI

20 

Cuzzocrea S, McDonald MC, Mota-Filipe H, Mazzon E, Costantino G, Britti D, Mazzullo G, Caputi AP and Thiemermann C: Beneficial effects of tempol, a membrane-permeable radical scavenger, in a rodent model of collagen-induced arthritis. Arthritis Rheum. 43:320–328. 2000. View Article : Google Scholar : PubMed/NCBI

21 

Di Paola R, Mazzon E, Zito D, Maiere D, Britti D, Genovese T and Cuzzocrea S: Effects of Tempol, a membrane-permeable radical scavenger, in a rodent model periodontitis. J Clin Periodontol. 32:1062–1068. 2005. View Article : Google Scholar : PubMed/NCBI

22 

Moosmann B and Behl C: Antioxidants as treatment for neurodegenerative disorders. Expert Opin Investig Drugs. 11:1407–1435. 2002. View Article : Google Scholar : PubMed/NCBI

23 

Grasbon-Frodl EM, Kösel S, Riess O, Müller U, Mehraein P and Graeber MB: Analysis of mitochondrial targeting sequence and coding region polymorphisms of the manganese superoxide dismutase gene in German Parkinson disease patients. Biochem Biophys Res Commun. 255:749–752. 1999. View Article : Google Scholar : PubMed/NCBI

24 

Schnackenberg CG and Wilcox CS: Two-week administration of tempol attenuates both hypertension and renal excretion of 8-Iso prostaglandin f2alpha. Hypertension. 33:424–428. 1999. View Article : Google Scholar : PubMed/NCBI

25 

Monti E, Supino R, Colleoni M, Costa B, Ravizza R and Gariboldi MB: Nitroxide TEMPOL impairs mitochondrial function and induces apoptosis in HL60 cells. J Cell Biochem. 82:271–276. 2001. View Article : Google Scholar : PubMed/NCBI

26 

Offer T, Russo A and Samuni A: The pro-oxidative activity of SOD and nitroxide SOD mimics. FASEB J. 14:1215–1223. 2000. View Article : Google Scholar : PubMed/NCBI

27 

Gariboldi MB, Rimoldi V, Supino R, Favini E and Monti E: The nitroxide tempol induced oxidative stress, p21WAF/CIP1, and cell death in HL60 cells. Free Radic Biol Med. 29:633–641. 2000. View Article : Google Scholar : PubMed/NCBI

28 

Agarwal R and Kaye SB: Ovarian cancer: Strategies for overcoming resistance to chemotherapy. Nat Rev Cancer. 3:502–516. 2003. View Article : Google Scholar : PubMed/NCBI

29 

Gariboldi MB, Lucchi S, Caserini C, Supino R, Oliva C and Monti E: Antiproliferative effect of the piperidine nitroxide TEMPOL on neoplastic and nonneoplastic mammalian cell lines. Free Radic Biol Med. 24:913–923. 1998. View Article : Google Scholar : PubMed/NCBI

30 

Perrone GG, Tan SX and Dawes IW: Reactive oxygen species and yeast apoptosis. Biochim Biophys Acta. 1783:1354–1368. 2008. View Article : Google Scholar : PubMed/NCBI

31 

Circu ML and Aw TY: Reactive oxygen species, cellular redox systems, and apoptosis. Free Radic Biol Med. 48:749–762. 2010. View Article : Google Scholar : PubMed/NCBI

32 

Todorova VK, Harms SA, Kaufmann Y, Luo S, Luo KQ, Babb K and Klimberg VS: Effect of dietary glutamine on tumor glutathione levels and apoptosis-related proteins in DMBA-induced breast cancer of rats. Breast Cancer Res Treat. 88:247–256. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Alpert E, Gruzman A, Totary H, Kaiser N, Reich R and Sasson S: A natural protective mechanism against hyperglycemia in vascular endothelial and smooth-muscle cells: Role of glucose and 12-hydroxyeicosatetraenoic acid. Biochem J. 362:413–422. 2002. View Article : Google Scholar : PubMed/NCBI

34 

Behrooz A and Ismail-Beigi F: Stimulation of glucose transport by hypoxia: Signals and mechanisms. News Physiol Sci. 14:105–110. 1999.PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Wang M, Li K, Zou Z, Li L, Zhu L, Wang Q, Gao W, Wang Y, Huang W, Liu R, Liu R, et al: Piperidine nitroxide Tempol enhances cisplatin‑induced apoptosis in ovarian cancer cells. Oncol Lett 16: 4847-4854, 2018.
APA
Wang, M., Li, K., Zou, Z., Li, L., Zhu, L., Wang, Q. ... Liu, Q. (2018). Piperidine nitroxide Tempol enhances cisplatin‑induced apoptosis in ovarian cancer cells. Oncology Letters, 16, 4847-4854. https://doi.org/10.3892/ol.2018.9289
MLA
Wang, M., Li, K., Zou, Z., Li, L., Zhu, L., Wang, Q., Gao, W., Wang, Y., Huang, W., Liu, R., Yao, K., Liu, Q."Piperidine nitroxide Tempol enhances cisplatin‑induced apoptosis in ovarian cancer cells". Oncology Letters 16.4 (2018): 4847-4854.
Chicago
Wang, M., Li, K., Zou, Z., Li, L., Zhu, L., Wang, Q., Gao, W., Wang, Y., Huang, W., Liu, R., Yao, K., Liu, Q."Piperidine nitroxide Tempol enhances cisplatin‑induced apoptosis in ovarian cancer cells". Oncology Letters 16, no. 4 (2018): 4847-4854. https://doi.org/10.3892/ol.2018.9289
Copy and paste a formatted citation
x
Spandidos Publications style
Wang M, Li K, Zou Z, Li L, Zhu L, Wang Q, Gao W, Wang Y, Huang W, Liu R, Liu R, et al: Piperidine nitroxide Tempol enhances cisplatin‑induced apoptosis in ovarian cancer cells. Oncol Lett 16: 4847-4854, 2018.
APA
Wang, M., Li, K., Zou, Z., Li, L., Zhu, L., Wang, Q. ... Liu, Q. (2018). Piperidine nitroxide Tempol enhances cisplatin‑induced apoptosis in ovarian cancer cells. Oncology Letters, 16, 4847-4854. https://doi.org/10.3892/ol.2018.9289
MLA
Wang, M., Li, K., Zou, Z., Li, L., Zhu, L., Wang, Q., Gao, W., Wang, Y., Huang, W., Liu, R., Yao, K., Liu, Q."Piperidine nitroxide Tempol enhances cisplatin‑induced apoptosis in ovarian cancer cells". Oncology Letters 16.4 (2018): 4847-4854.
Chicago
Wang, M., Li, K., Zou, Z., Li, L., Zhu, L., Wang, Q., Gao, W., Wang, Y., Huang, W., Liu, R., Yao, K., Liu, Q."Piperidine nitroxide Tempol enhances cisplatin‑induced apoptosis in ovarian cancer cells". Oncology Letters 16, no. 4 (2018): 4847-4854. https://doi.org/10.3892/ol.2018.9289
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