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 Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
November-2016 Volume 36 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-2016 Volume 36 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

Rapamycin and fructose-1,6-bisphosphate reduce the HEPG2 cell proliferation via increase of free radicals and apoptosis

  • Authors:
    • Elisa Feller Gonçalves da Silva
    • Gabriele Catyana Krause
    • Kelly Goulart Lima
    • Gabriela Viegas Haute
    • Leonardo Pedrazza
    • Fernanda Cristina Mesquita
    • Bruno Souza Basso
    • Anderson Catarina Velasquez
    • Fernanda Bordignon Nunes
    • Jarbas Rodrigues de Oliveira
  • View Affiliations / Copyright

    Affiliations: Laboratory of Cellular Biophysics and Inflammation, Department of Cellular and Molecular Biology, School of Biosciences, Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Porto Alegre, Rio Grande do Sul, CEP 90619‑900, Brazil
  • Pages: 2647-2652
    |
    Published online on: September 20, 2016
       https://doi.org/10.3892/or.2016.5111
  • 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

Hepatocellular carcinoma is the most prevalent type of tumor among primary tumors affecting the liver. Rapamycin is currently used as a basis for chemotherapy in the treatment of cancers, including the liver. Because it shows several adverse effects, minimizing these effects without compromising efficacy is important. In this sense other drugs may be used concomitantly. One of these drugs is fructose-1,6-bisphosphate (FBP), which has shown therapeutic effect in various pathological situations, having antioxidant and anti-inflammatory proprieties. The objective of the present study was to evaluate the activity of rapamycin in combination with the FBP in HepG2 cell proliferation and the mechanisms involved. HepG2 cells were analyzed after 72 h of treatment with both drugs. Cell proliferation, cytotoxicity, cytokines, apoptosis, senescence, autophagy and oxidative stress were accessed. Ιt was demonstrated that the combination is more efficient than the single use of substances, because subtherapeutic doses of rapamycin, when associated to FBP become effective, reducing cell proliferation, through a significant increase in the production of tiobarbituric acid reactive substances (TBARS), suggesting that this might be the cause of death by apoptosis. According to these results, we believe that the association of both drugs may be a promising choice for the treatment of hepatocarcinoma.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

View References

1 

Organization WHO: The top 10 causes of death. Journal. 2014.

2 

Gonzalez SA: Novel biomarkers for hepatocellular carcinoma surveillance: Has the future arrived? Hepatobiliary Surg Nutr. 3:410–414. 2014.

3 

Baird A, Lee J, Podvin S, Kurabi A, Dang X, Coimbra R, Costantini T, Bansal V and Eliceiri BP: Esophageal cancer-related gene 4 at the interface of injury, inflammation, infection, and malignancy. Gastrointest Cancer. 2014:131–142. 2014. View Article : Google Scholar

4 

Capece D, Fischietti M, Verzella D, Gaggiano A, Cicciarelli G, Tessitore A, Zazzeroni F and Alesse E: The inflammatory micro-environment in hepatocellular carcinoma: A pivotal role for tumor-associated macrophages. Biomed Res Int. 2013:1872042013. View Article : Google Scholar

5 

Bharadwaj S and Gohel TD: Perspectives of physicians regarding screening patients at risk of hepatocellular carcinoma. Gastroenterol Rep (Oxf) gou089. 2015.

6 

Salhab M and Canelo R: An overview of evidence-based management of hepatocellular carcinoma: A meta-analysis. J Cancer Res Ther. 7:463–475. 2011. View Article : Google Scholar

7 

Almeida JRCd: Farmacêuticos em Oncologia: uma nova realidade. Atheneu; Aracaju: pp. 3582004, In Portuguese.

8 

Wang Z, Zhou J, Fan J, Qiu SJ, Yu Y, Huang XW and Tang ZY: Effect of rapamycin alone and in combination with sorafenib in an orthotopic model of human hepatocellular carcinoma. Clin Cancer Res. 14:5124–5130. 2008. View Article : Google Scholar : PubMed/NCBI

9 

Wang Z, Zhou J, Fan J, Tan CJ, Qiu SJ, Yu Y, Huang XW and Tang ZY: Sirolimus inhibits the growth and metastatic progression of hepatocellular carcinoma. J Cancer Res Clin Oncol. 135:715–722. 2009. View Article : Google Scholar

10 

Wang C, Gao D, Guo K, Kang X, Jiang K, Sun C, Li Y, Sun L, Shu H, Jin G, et al: Novel synergistic antitumor effects of rapamycin with bortezomib on hepatocellular carcinoma cells and orthotopic tumor model. BMC Cancer. 12:1662012. View Article : Google Scholar : PubMed/NCBI

11 

Wang Y, Speeg KV, Washburn WK and Halff G: Sirolimus plus sorafenib in treating HCC recurrence after liver transplantation: A case report. World J Gastroenterol. 16:5518–5522. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Wang J: 203985 Everolimus Clinpharm BPCA. 2012, http://www.fda.gov/downloads/drugs/developmentapprovalprocess/developmentresources/ucm320466.pdf. Accessed February 11, 2016.

13 

Zirkelbach JF: 22088 Temsirolimus Clinpharm BPCA. 2011, http://www.fda.gov/downloads/drugs/developmentapprovalprocess/developmentresources/ucm307049.pdf. Accessed February 11, 2016.

14 

Porta C, Paglino C and Mosca A: Targeting PI3K/Akt/mTOR Signaling in Cancer. Front Oncol. 4:642014. View Article : Google Scholar : PubMed/NCBI

15 

Sahin F, Kannangai R, Adegbola O, Wang J, Su G and Torbenson M: mTOR and P70 S6 kinase expression in primary liver neoplasms. Clin Cancer Res. 10:8421–8425. 2004. View Article : Google Scholar : PubMed/NCBI

16 

Cuconati A, Mills C, Goddard C, Zhang X, Yu W, Guo H, Xu X and Block TM: Suppression of AKT anti-apoptotic signaling by a novel drug candidate results in growth arrest and apoptosis of hepatocellular carcinoma cells. PLoS One. 8:e545952013. View Article : Google Scholar : PubMed/NCBI

17 

Cendales L, Bray R, Gebel H, Brewster L, Elbein R, Farthing D, Song M, Parker D, Stillman A, Pearson T, et al: Tacrolimus to belatacept conversion following hand transplantation: A case report. Am J Transplant. 15:2250–2255. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Seok SM, Park TY, Park HS, Baik EJ and Lee SH: Fructose-1,6-bisphosphate suppresses lipopolysaccharide-induced expression of ICAM-1 through modulation of toll-like receptor-4 signaling in brain endothelial cells. Int Immunopharmacol. 26:203–211. 2015. View Article : Google Scholar : PubMed/NCBI

19 

Zhang JF, Liu JJ, Lu MQ, Cai CJ, Yang Y, Li H, Xu C and Chen GH: Rapamycin inhibits cell growth by induction of apoptosis on hepatocellular carcinoma cells in vitro. Transpl Immunol. 17:162–168. 2007. View Article : Google Scholar : PubMed/NCBI

20 

Dai ZJ, Gao J, Ma XB, Kang HF, Wang BF, Lu WF, Lin S, Wang XJ and Wu WY: Antitumor effects of rapamycin in pancreatic cancer cells by inducing apoptosis and autophagy. Int J Mol Sci. 14:273–285. 2012. View Article : Google Scholar

21 

Philipp AB, Nagel D, Stieber P, Lamerz R, Thalhammer I, Herbst A and Kolligs FT: Circulating cell-free methylated DNA and lactate dehydrogenase release in colorectal cancer. BMC Cancer. 14:2452014. View Article : Google Scholar : PubMed/NCBI

22 

Human Inflammatory Cytokines Kit Instruction Manual. Journal. 2008, http://www.bdbiosciences.com/documents/CBA_Human_Inf_Cytokine_manual.pdf. Accessed February 11, 2016.

23 

Kim TM, Shin SK, Kim TW, Youm SY, Kim DJ and Ahn B: Elm tree bark extract inhibits HepG2 hepatic cancer cell growth via pro-apoptotic activity. J Vet Sci. 13:7–13. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Chiela ECF: Protocol for measuring autophagy. Journal. http://www.ufrgs.br/labsinal/autofagia.htm. Accessed February 11, 2016.

25 

Nepal S and Park PH: Regulatory role of autophagy in globular adiponectin-induced apoptosis in cancer cells. Biomol Ther (Seoul). 22:384–389. 2014. View Article : Google Scholar

26 

Carlos SP, Dias AS, Forgiarini Júnior LA, Patricio PD, Graciano T, Nesi RT, Valença S, Chiappa AM, Cipriano G JR, Souza CT, et al: Oxidative damage induced by cigarette smoke exposure in mice: impact on lung tissue and diaphragm muscle. J Bras Pneumol. 40:411–420. 2014. View Article : Google Scholar : PubMed/NCBI

27 

Rutkowski MR and Conejo-Garcia JR: Size does not matter: Commensal microorganisms forge tumor-promoting inflammation and anti-tumor immunity. Oncoscience. 2:239–246. 2015. View Article : Google Scholar : PubMed/NCBI

28 

Asnaghi L, Bruno P, Priulla M and Nicolin A: mTOR: A protein kinase switching between life and death. Pharmacol Res. 50:545–549. 2004. View Article : Google Scholar : PubMed/NCBI

29 

McGranahan N, Favero F, De Bruin EC, Birkbak NJ, Szallasi Z and Swanton C: Clonal status of actionable driver events and the timing of mutational processes in cancer evolution. Sci Transl Med. 7:283ra542015. View Article : Google Scholar : PubMed/NCBI

30 

Fervenza FC, Fitzpatrick PM, Mertz J, Erickson SB, Liggett S, Popham S, Wochos DN, Synhavsky A, Hippler S, Larson TS, et al Mayo Nephrology Collaborative Committee: Acute rapamycin nephrotoxicity in native kidneys of patients with chronic glomerulopathies. Nephrol Dial Transplant. 19:1288–1292. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Azambuja AA, Lunardelli A, Nunes FB, Gaspareto PB, Donadio MV, Poli de Figueiredo CE and de Oliveira JR: Effect of fructose-1,6-bisphosphate on the nephrotoxicity induced by cisplatin in rats. Inflammation. 34:67–71. 2011. View Article : Google Scholar

32 

Seelaender M, Neto JC, Pimentel GD, Goldszmid RS and Lira FS: Inflammation in the disease: Mechanism and therapies 2014. Mediators Inflamm. 2015:1698522015. View Article : Google Scholar : PubMed/NCBI

33 

Raza H, John A and Benedict S: Acetylsalicylic acid-induced oxidative stress, cell cycle arrest, apoptosis and mitochondrial dysfunction in human hepatoma HepG2 cells. Eur J Pharmacol. 668:15–24. 2011. View Article : Google Scholar : PubMed/NCBI

34 

Goswami B, Rajappa M, Mallika V, Shukla DK and Kumar S: TNF-alpha/IL-10 ratio and C-reactive protein as markers of the inflammatory response in CAD-prone North Indian patients with acute myocardial infarction. Clin Chim Acta. 408:14–18. 2009. View Article : Google Scholar : PubMed/NCBI

35 

Raouf S, Weston C and Yucel N: Reproducibility Project: Cancer Biology: Registered report: Senescence surveillance of pre-malignant hepatocytes limits liver cancer development. Elife. Jan 26–2015. View Article : Google Scholar

36 

Vessoni AT, Filippi-Chiela EC, Menck CF and Lenz G: Autophagy and genomic integrity. Cell Death differ. 20:1444–1454. 2013. View Article : Google Scholar : PubMed/NCBI

37 

Suzuki K and Matsubara H: Recent advances in p53 research and cancer treatment. J BioMed Biotechnol. 2011:9783122011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
da Silva EF, Krause GC, Lima KG, Haute GV, Pedrazza L, Mesquita FC, Basso BS, Velasquez AC, Nunes FB, de Oliveira JR, de Oliveira JR, et al: Rapamycin and fructose-1,6-bisphosphate reduce the HEPG2 cell proliferation via increase of free radicals and apoptosis. Oncol Rep 36: 2647-2652, 2016.
APA
da Silva, E.F., Krause, G.C., Lima, K.G., Haute, G.V., Pedrazza, L., Mesquita, F.C. ... de Oliveira, J.R. (2016). Rapamycin and fructose-1,6-bisphosphate reduce the HEPG2 cell proliferation via increase of free radicals and apoptosis. Oncology Reports, 36, 2647-2652. https://doi.org/10.3892/or.2016.5111
MLA
da Silva, E. F., Krause, G. C., Lima, K. G., Haute, G. V., Pedrazza, L., Mesquita, F. C., Basso, B. S., Velasquez, A. C., Nunes, F. B., de Oliveira, J. R."Rapamycin and fructose-1,6-bisphosphate reduce the HEPG2 cell proliferation via increase of free radicals and apoptosis". Oncology Reports 36.5 (2016): 2647-2652.
Chicago
da Silva, E. F., Krause, G. C., Lima, K. G., Haute, G. V., Pedrazza, L., Mesquita, F. C., Basso, B. S., Velasquez, A. C., Nunes, F. B., de Oliveira, J. R."Rapamycin and fructose-1,6-bisphosphate reduce the HEPG2 cell proliferation via increase of free radicals and apoptosis". Oncology Reports 36, no. 5 (2016): 2647-2652. https://doi.org/10.3892/or.2016.5111
Copy and paste a formatted citation
x
Spandidos Publications style
da Silva EF, Krause GC, Lima KG, Haute GV, Pedrazza L, Mesquita FC, Basso BS, Velasquez AC, Nunes FB, de Oliveira JR, de Oliveira JR, et al: Rapamycin and fructose-1,6-bisphosphate reduce the HEPG2 cell proliferation via increase of free radicals and apoptosis. Oncol Rep 36: 2647-2652, 2016.
APA
da Silva, E.F., Krause, G.C., Lima, K.G., Haute, G.V., Pedrazza, L., Mesquita, F.C. ... de Oliveira, J.R. (2016). Rapamycin and fructose-1,6-bisphosphate reduce the HEPG2 cell proliferation via increase of free radicals and apoptosis. Oncology Reports, 36, 2647-2652. https://doi.org/10.3892/or.2016.5111
MLA
da Silva, E. F., Krause, G. C., Lima, K. G., Haute, G. V., Pedrazza, L., Mesquita, F. C., Basso, B. S., Velasquez, A. C., Nunes, F. B., de Oliveira, J. R."Rapamycin and fructose-1,6-bisphosphate reduce the HEPG2 cell proliferation via increase of free radicals and apoptosis". Oncology Reports 36.5 (2016): 2647-2652.
Chicago
da Silva, E. F., Krause, G. C., Lima, K. G., Haute, G. V., Pedrazza, L., Mesquita, F. C., Basso, B. S., Velasquez, A. C., Nunes, F. B., de Oliveira, J. R."Rapamycin and fructose-1,6-bisphosphate reduce the HEPG2 cell proliferation via increase of free radicals and apoptosis". Oncology Reports 36, no. 5 (2016): 2647-2652. https://doi.org/10.3892/or.2016.5111
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