Apoptosis Mechanisms Related to the Increased Sensitivity of Jurkat T-cells vs A431 Epidermoid Cells to Photodynamic Therapy with the Phthalocyanine Pc 4

Authors

  • Malcolm S. Ke,

    1. Department of Dermatology, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
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  • Liang-yan Xue,

    1. Department of Radiation Oncology, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
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  • Denise K. Feyes,

    1. Department of Dermatology, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
    2. Department of Radiation Oncology, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
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  • Kashif Azizuddin,

    1. Department of Radiation Oncology, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
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  • Elma D. Baron,

    1. Department of Dermatology, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
    2. Skin Diseases Research Center, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
    3. Case Comprehensive Cancer Center, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
    4. Dermatology Service, Louis Stokes Department of Veterans Affairs Medical Center, Cleveland, OH
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  • Thomas S. McCormick,

    1. Department of Dermatology, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
    2. Skin Diseases Research Center, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
    3. Case Comprehensive Cancer Center, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
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  • Hasan Mukhtar,

    1. Department of Dermatology, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
    2. Skin Diseases Research Center, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
    3. Case Comprehensive Cancer Center, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
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    • §

      Current address: Hasan Mukhtar, Department of Dermatology, University of Wisconsin, Madison, WI, USA.

  • Ashok Panneerselvam,

    1. Department of Epidemiology and Biostatistics, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
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  • Mark D. Schluchter,

    1. Case Comprehensive Cancer Center, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
    2. Department of Epidemiology and Biostatistics, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
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  • Kevin D. Cooper,

    1. Department of Dermatology, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
    2. Skin Diseases Research Center, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
    3. Case Comprehensive Cancer Center, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
    4. Dermatology Service, Louis Stokes Department of Veterans Affairs Medical Center, Cleveland, OH
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  • Nancy L. Oleinick,

    Corresponding author
    1. Department of Radiation Oncology, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
    2. Skin Diseases Research Center, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
    3. Case Comprehensive Cancer Center, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
      *Corresponding author email: nlo@case.edu (Nancy L. Oleinick)
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  • Seth R. Stevens

    1. Department of Dermatology, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
    2. Skin Diseases Research Center, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
    3. Case Comprehensive Cancer Center, University Hospitals Case Medical Center and Case Western Reserve University, Cleveland, OH
    4. Dermatology Service, Louis Stokes Department of Veterans Affairs Medical Center, Cleveland, OH
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    • Current address: Seth R. Stevens, Amgen, Incorporated, Thousand Oaks, CA, USA.

Errata

This article is corrected by:

  1. Errata: Apoptosis Mechanisms Related to the Increased Sensitivity of Jurkat T-cells versus A431 Epidermoid Cells to Photodynamic Therapy with the Phthalocyanine Pc 4 Volume 84, Issue 3, 819, Article first published online: 21 March 2008

  • This paper is part of a special issue dedicated to Professor Hasan Mukhtar on the occasion of his 60th birthday.

  • Presented in part at the Society for Investigative Dermatology, May 15–18, 2002, Los Angeles, CA, USA.

*Corresponding author email: nlo@case.edu (Nancy L. Oleinick)

Abstract

To examine the clinical applicability of Pc 4, a promising second-generation photosensitizer, for the photodynamic treatment of lymphocyte-mediated skin diseases, we studied the A431 and Jurkat cell lines, commonly used as surrogates for human keratinocyte-derived carcinomas and lymphocytes, respectively. As revealed by ethyl acetate extraction and absorption spectrophotometry, uptake of Pc 4 into the two cell lines was linear with Pc 4 concentration and similar on a per cell basis but greater in Jurkat cells on a per mass basis. Flow cytometry showed that uptake was linear at low doses; variations in the dose–response for uptake measured by fluorescence supported differential aggregation of Pc 4 in the two cell types. As detected by confocal microscopy, Pc 4 localized to mitochondria and endoplasmic reticulum in both cell lines. Jurkat cells were much more sensitive to the lethal effects of phthalocyanine photodynamic therapy (Pc 4-PDT) than were A431 cells, as measured by a tetrazolium dye reduction assay, and more readily underwent morphological apoptosis. In a search for molecular factors to explain the greater photosensitivity of Jurkat cells, the fate of important Bcl-2 family members was monitored. Jurkat cells were more sensitive to the induction of immediate photodamage to Bcl-2, but the difference was insufficient to account fully for their greater sensitivity. The antiapoptotic protein Mcl-1 was extensively cleaved in a dose- and caspase-dependent manner in Jurkat, but not in A431, cells exposed to Pc 4-PDT. Thus, the greater killing by Pc 4-PDT in Jurkat compared with A431 cells correlated with greater Bcl-2 photodamage and more strongly to the more extensive Mcl-1 degradation. Pc 4-PDT may offer therapeutic advantages in targeting inflammatory cells over normal keratinocytes in the treatment of T-cell-mediated skin diseases, such as cutaneous lymphomas, dermatitis, lichenoid tissue reactions and psoriasis, and it will be instructive to evaluate the role of Bcl-2 family proteins, especially Mcl-1, in the therapeutic response.

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