Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letters to the Editor
  • Published:

Avoiding premature apoptosis of normal epidermal cells

Nature Medicine volume 7, pages 385–386 (2001)Cite this article

To the editor

The article by Jo et al., in the May 2000 issue of Nature Medicine1, raised a cautionary note for the use of tumor necrosis factor-related apoptosis-inducing ligand (Apo2L/TRAIL) in human cancer therapy2,3. By producing a polyhistidine-tagged recombinant soluble version of Apo2L/TRAIL (Apo2L/TRAIL.His), these investigators observed induction of apoptosis using cultured normal human hepatocytes. In addition, a previous group using a recombinant soluble version of the ligand (amino acids 95–281) fused to trimerizing leucine zipper (LZ-Apo2L/TRAIL), also noted that normal human keratinocytes (KCs) were sensitive to this preparation4. To further explore the potential safety of using apoptosis-inducing ligands in cutaneous oncology5, we performed a study to directly compare apoptosis-inducing potencies for a recombinant soluble, native-sequence (amino acids 114–281) non-tagged version (that is, NT-Apo2L/TRAIL)6, to the other 2 preparations using normal KCs and a transformed KC-cell line, HaCaT cells.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Induction of KC cell death is dependent on the type of Apo2L/TRAIL preparation used to trigger apoptosis.
Figure 2: Relative sensitivity of keratinocytes versus HaCaT cells to various Apo2L/TRAIL preparations.

References

  1. Jo, M. et al. Apoptosis induced in normal human hepatocytes by tumor necrosis factor- related apoptosis-inducing ligand. Nature Med. 6, 564–567 (2000).

    Article  CAS  Google Scholar 

  2. Nagata, S. Steering anti-cancer drugs away from the TRAIL. Nature Med. 6: 502–503 (2000).

    Article  CAS  Google Scholar 

  3. Gura, T. Caution raised about possible new drug. Science 288, 786–787 (2000).

    Article  CAS  Google Scholar 

  4. Leverkus, M. et al. Regulation of tumor necrosis factor-related apoptosis-inducing ligand sensitivity in primary and transformed human keratinocytes. Cancer Res. 60, 553–559 (2000).

    CAS  PubMed  Google Scholar 

  5. Thompson, C.B. Apoptosis in the pathogenesis and treatment of disease. Science 267, 1456–1462 (1999).

    Article  Google Scholar 

  6. Ashkenazi, A. et al. Safety and antitumor activity of recombinant soluble Apo2 ligand. J. Clin. Invest. 104, 155–162 (1999).

    Article  CAS  Google Scholar 

  7. Griffith, T.S. et al. Intracellular regulation of TRAIL-induced apoptosis in human melanoma cells. J. Immunol. 161, 2833–2840 (1998).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Loyola University Medical Center, Cardinal Bernardin Cancer Center, Maywood, Illinois, USA

    Jian-zhong Qin, Vijaya Chaturvedi, Brian Bonish & Brian J. Nickoloff

Authors
  1. Jian-zhong Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vijaya Chaturvedi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Brian Bonish
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Brian J. Nickoloff
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Qin, Jz., Chaturvedi, V., Bonish, B. et al. Avoiding premature apoptosis of normal epidermal cells. Nat Med 7, 385–386 (2001). https://doi.org/10.1038/86401

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/86401

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing