Tumor Biology

, Volume 35, Issue 5, pp 4539–4544 | Cite as

The study of inducing apoptosis effect of fructose 1,6-bisphosphate on the papillary thyroid carcinoma cell and its related mechanism

  • Yan Li
  • Wei Wei
  • Hu-Wei Shen
  • Wen-Qing Hu
Research Article


This study aims to investigate the apoptosis-inducing effect of fructose 1,6-bisphosphate (F1,6BP) on the related mechanism of papillary thyroid carcinoma W3 and T cells. W3 cells were treated with F1,6BP alone or in combination with antioxidant catalase (CAT) or N-acetyl-l-cysteine (NAC). The changes of cell viability and cell nucleus morphology were examined by cell proliferation assay and Hoechst staining, and apoptosis levels of these cells were measured with flow cytometry. The changes of reactive oxygen species (ROS) level and the percentage of oxidized glutathione in total glutathione in W3 cells were detected by 2′,7′-dichlorodihydrofluorescein diacetate (DCFH-DA) staining or colorimetry assay. At the same time, real-time fluorescence quantitative PCR was adopted to evaluate the expression levels of CAT and glutathione peroxidase (GSH-Px) mRNAs in W3 cells. F1,6BP inhibited the growth of W3 cells significantly, coupling with an increase in intracellular ROS level and the percentage of oxidized glutathione in total glutathione. Typical apoptotic morphological changes of the cell nucleus happened. The apoptosis rate and GSH-Px and CAT mRNAs expression levels were upregulated after F1,6BP treatment. The antitumor effect of F1,6BP was significantly decreased after W3 cells were pretreated with NAC and CAT. F1,6BP can induce the apoptosis of W3 cells through upregulating the generation of ROS, especially the production of H2O2.


Papillary thyroid carcinoma Fructose 1,6-bisphosphate ROS H2O2 


Conflicts of interest



  1. 1.
    Aschebrook-Kilfoy B, Ward MH, Sabra MM, Devesa SS. Thyroid cancer incidence patterns in the United States by histologic type, 1992–2006. Thyroid. 2011;21(2):125–34.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    De Raedt T, Walton Z, Yecies JL, Li D, Chen Y, Malone CF, et al. Exploiting cancer cell vulnerabilities to develop a combination therapy for Ras-driven tumors. Cancer Cell. 2011;20(3):400–13.CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Mauro C, Leow SC, Anso E, Rocha S, Thotakura AK, Tornatore L, et al. NF-κB controls energy homeostasis and metabolic adaptation by up-regulating mitochondrial respiration. Nat Cell Biol. 2011;13(10):1272–9.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Lian XY, Khan FA, Stringer JL. Fructose-1,6-bisphosphate has anticonvulsant activity in models of acute seizures in adult rats. J Neurosci. 2007;27(44):12007–11.CrossRefPubMedGoogle Scholar
  5. 5.
    Liu D, Zhang H, Gu W, Liu Y, Zhang M. Neuroprotective effects of ginsenoside Rb1 on high glucose-induced neurotoxicity in primary cultured rat hippocampal neurons. PLoS One. 2013;8(11):e79399.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Kang C, Lee H, Hah DY, Heo JH, Kim CH, Kim E, et al. Protective effects of Houttuynia cordata Thunb. on gentamicin-induced oxidative stress and nephrotoxicity in rats. Toxicol Res. 2013;29(1):61–7.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Trachootham D, Zhou Y, Zhang H, Demizu Y, Chen Z, Pelicano H, et al. Selective killing of oncogenically transformed cells through a ROS-mediated mechanism by beta-phenylethyl isothiocyanate. Cancer Cell. 2006;10(3):241–52.CrossRefPubMedGoogle Scholar
  8. 8.
    Chen W, Zhao Z, Li L, Wu B, Chen SF, Zhou H, et al. Hispolon induces apoptosis in human gastric cancer cells through a ROS-mediated mitochondrial pathway. Free Radio Biol Med. 2008;45(1):60–72.CrossRefGoogle Scholar
  9. 9.
    Schumacker PT. Reactive oxygen species in cancer cells: live by the sword, die by the sword. Cancer Cell. 2006;10(3):175–6.CrossRefPubMedGoogle Scholar
  10. 10.
    Pongrakhananon V, Chunhacha P, Chanvorachote P. Ouabain suppresses the migratory behavior of lung cancer cells. PLoS One. 2013;8(7):e68623.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Jeon SM, Hay N. The dark face of AMPK as an essential tumor promoter. Cell Logist. 2012;2(4):197–202.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Perera RM, Bardeesy N. Cancer: when antioxidants are bad. Nature. 2011;475(7354):43–4.CrossRefPubMedGoogle Scholar
  13. 13.
    Lian XY, Khan FA, Stringer JL. Fructose-1,6-bisphosphate has anticonvulsant activity in models of acute seizures in adult rats. J Neurosci. 2007;27(44):12007–11.CrossRefPubMedGoogle Scholar
  14. 14.
    Cuesta E, Boada J, Calafell R, Perales JC, Roig T, Bermudez J. Fructose 1,6-bisphosphate prevented endotoxemia, macrophage activation, and liver injury induced by d-galactosamine in rats. Crit Care Med. 2006;34(3):807–14.CrossRefPubMedGoogle Scholar
  15. 15.
    Alva N, Cruz D, Sanchez S, Valentín JM, Bermudez J, Carbonell T. Nitric oxide as a mediator of fructose 1,6-bisphosphate protection in galactosamine-induced hepatotoxicity in rats. Nitric Oxide. 2013;28:17–23.CrossRefPubMedGoogle Scholar
  16. 16.
    Burlacu A, Jinga V, Gafencu AV, Simionescu M. Severity of oxidative stress generates different mechanisms of endothelial cell death. Cell Tissue Res. 2001;306(3):409–16.CrossRefPubMedGoogle Scholar
  17. 17.
    Yao CW, Piao MJ, Kim KC, Zheng J, Cha JW, Hyun JW. 6′-O-Galloylpaeoniflorin protects human keratinocytes against oxidative stress-induced cell damage. Biomol Ther (Seoul). 2013;21(5):349–57.CrossRefGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  1. 1.Department of EndocrinologyHeping Hospital Affiliated to Changzhi Medical CollegeChangzhiChina
  2. 2.Department of General SurgeryHeji Hospital Affiliated to Changzhi Medical CollegeChangzhiChina

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