[go: up one dir, main page]
More Web Proxy on the site http://driver.im/
Skip to main content

Advertisement

Wortmannin induced apoptosis of leukemia cells by reducing PI3K/Akt

  • Published:
The Chinese-German Journal of Clinical Oncology

Abstract

Objective

We studied the effects of Wortmannin (WM) on the proliferation and apoptosis of leukemia cells, and explore the possible mechanisms.

Methods

The human myeloid leukemia cell line K562 was treated with different concentrations of WM, and then detected the activity of the cell proliferation by MTT assay, comet tail formation of cell DNA damage phenomenon by single cell gel electrophoresis, cell apoptosis by Annexin V-FITC/PI double staining and the expression levels of total Akt, phoshorylated Akt, NF-κB and protein in K562 cell by Western blotting, RT-PCR test before and after WM.

Results

WM inhibited cell proliferation of K562 in a concentration-dependent manner, with IC50 value for 24 h being 25 nmol/L. WM induced apoptosis of K562 cells in a concentration-dependent manner, and could induce the breakage of DNA strand of K562 cell. The rate of DNA tail and the tail length of experimental groups were significantly higher than that of control group. WM may inhibit the expression of phosphorylated Akt and NF-KB protein in a dose-dependent manner in both the protein and gene levels, but no significant effect on total Akt protein.

Conclusion

WM inhibited cell proliferation and induced apoptosis in K562 and concentration-dependent manner. The possible mechanism may be involved in the regulation of survival signaling pathway, such as PI3K/Akt/Nκ-KB.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
£29.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (United Kingdom)

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Olsen BB, Bjøorling-Poulsen M, Guerra B. Emodin negatively affects the phosphoinositide 3-kinase/AKT signalling pathway: a study on its mechanism of action. Int J Biochem Cell Biol, 2007, 39: 227–237.

    Article  CAS  PubMed  Google Scholar 

  2. Rudelius M, Pittaluga S, Nishizuka S, et al. Constitutive activation of Akt contributes to the pathogenesis and survival of mantle cell lymphoma. Blood, 2006, 108: 1668–1676.

    Article  CAS  PubMed  Google Scholar 

  3. Tazzari PL, Cappellini A, Ricci F, et al. Multidrug resistance-associated protein 1 expression is under the control of the phosphoinositide 3 kinase/Akt signal transduction network in human acute myelogenous leukemia blasts. Leukemia, 2007, 21: 427–438.

    Article  CAS  PubMed  Google Scholar 

  4. Priulla M, Calastretti A, Bruno P, et al. Preferential chemosensitization of PTEN-mutated prostate cells by silencing the Akt kinase. Prostate, 2007, 67: 782–789.

    Article  CAS  PubMed  Google Scholar 

  5. Martelli AM, Nyakern M, Tabellini G, et al. Phosphoinositide 3-kinase/Akt signaling pathway and its theraeutical implications for human acute myeloid leukemia. Leukemia, 2006, 20: 911–928.

    Article  CAS  PubMed  Google Scholar 

  6. Tang JM, He QY, Guo RX, et al. Phosphorylated Akt overexpression and loss of PTEN expression in non-small cell lung cancer confers poor prognosis. Lung Cancer, 2006, 51: 181–191.

    Article  PubMed  Google Scholar 

  7. Wu H, Weng D, Xing H. Reversal of multidrug resistance and inhibition of phosphorylation of AKT in human ovarian cancer cell line by wild-type PTEN gene. J Huazhong Univ Sci Technolg (Chinese), 2007, 27: 713–716.

    Article  CAS  Google Scholar 

  8. Zhang D, Fan D. Muhidrug resistance in gastric cancer: recent research advances and ongoing therapeutic challenges. Expert Rev Anticancer Ther, 2007, 7: 1369–1378.

    Article  CAS  PubMed  Google Scholar 

  9. Wang XF, Xing ML, Shen Y, et al. Oral administration of Cr (VI) induced oxidative stress, DNA damage and apoptotic cell death in mice. Toxicology, 2006, 228: 16–23.

    Article  CAS  PubMed  Google Scholar 

  10. Huang XL, Cui GH, Zhou KY. Correlation of P13K-Akt signal pathway to apoptosis of tumor cells. Chin J Cancer (Chinese), 2008, 27: 331–336.

    CAS  Google Scholar 

  11. Wu C, Huang J. Phosphatidylinositol 3-kinase-AKT-mammalian target of rapamycin pathway is essential for neuroendocrine differentiation of prostate cancer. J Biol Chem, 2007, 282: 3571–3583.

    Article  CAS  PubMed  Google Scholar 

  12. Zeng HM, Wang DH, Liu WX. PI3K/Akt pathway and tumor therapy. Chin J Cancer Biother (Chinese), 2008, 15: 82–85.

    CAS  Google Scholar 

  13. Wang Y, Jiang XY, Liu L, et al. Phosphatidylinositol 3-kinase/Akt pathway regulates hepatic stellate cell apoptosis. World J Gastroenterol (Chinese), 2008, 14: 5186–5191.

    Article  CAS  Google Scholar 

  14. Liang ZL, Kuang XC, Wen GM, et al. Observation on apoptosis of the rats with acute renal failure. J Guangxi Med Univ (Chinese), 2008, 25: 25–26.

    CAS  Google Scholar 

  15. Liu FC, He YW, Yu FD. Mechanism of diammonium glycyrrhizinate entericcoated capsules in alleviating hepatocytic injury in mice with acute liver failure. World Chin J Digestol (Chinese), 2009, 17: 1014–1017.

    CAS  Google Scholar 

  16. Xie X, Gao Q, Wang YL, et al. Inhibition of PI3 K/PKB signal pathway improves chemotherapeutic effect on gastric carcinoma cell lines. Chin Pharmacol Bull (Chinese), 2008, 24: 1666–1670.

    CAS  Google Scholar 

  17. Han Z, Hong L, Han Y, et al. Phospho Akt mediates muhidrug resistance of gastric cancer cells through regulation of P-gP, Bcl-2 and Bax. J Exp Clin Cancer Res (Chinese), 2007, 26: 261–268.

    CAS  Google Scholar 

  18. Lee CH, Jeon YT, Kim SH, et al. NF-kappaB as a potential molecular target for cancer therapy. Biofactors, 2007, 29: 19–35.

    Article  CAS  PubMed  Google Scholar 

  19. Ohta T, Ohnfiehi M, Hayasaka T, et al. Inhibition of phosphatidylinositol 3-kinase increases efficacy of cisplatin in vitro ovarian cancer models. Endocrinology, 2006, 147: 1761–1179.

    Article  CAS  PubMed  Google Scholar 

  20. Poh TW, Pervaiz S. LY294002 and LY303511 sensitize tumor cells to drug-induced apoptosis via intracellular hydrogenperoxide production independent of the phosphoinositide 3-kinase-Akt pathway. Cancer Res, 2005, 65: 6264–6274.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Xiaonan Wang.

Additional information

Supported by a grant from the Hubei Province Natural Science Foundation of China (No. 200511008).

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, X., Wu, Q., Zhang, L. et al. Wortmannin induced apoptosis of leukemia cells by reducing PI3K/Akt. Chin. -Ger. J. Clin. Oncol. 9, 734–738 (2010). https://doi.org/10.1007/s10330-010-0715-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10330-010-0715-1

Key words