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Proceedings Paper

Molecular factors in cell (and tumor) response to photodynamic therapy: the role of Bid
Author(s): Song-mao Chiu; Liang-yan Xue; Minh Lam; Myriam E. Rodriguez; Ping Zhang; Malcolm E. Kenney; Anna-Liisa Nieminen; Nancy L. Oleinick
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Paper Abstract

The phthalocyanine photosensitizer Pc 4 binds preferentially to mitochondrial and endoplasmic reticulum membranes. Upon photoirradiation of Pc 4-loaded cells, membrane components, including Bcl-2, are photodamaged and apoptosis is triggered. We recently prepared analogues of Pc 4 containing two axial ligands, one identical to the single ligand in Pc 4, and the other containing one or two hydroxyl groups on a dimethylsiloxy alkyl chain. Pc 181 is representative of this group of photosensitizers. In MCF-7 human breast cancer cells, the new analogues preferentially localized in lysosomes and were highly efficient in inducing apoptosis and overall cell death. The Bcl-2 family member Bid is required for signaling to mitochondria for apoptosis in response to primary lysosomal photodamage. To further evaluate the role of Bid, we compared the effects of PDT with Pc 4 or Pc 181 in wild-type murine embryonic fibroblasts and those knocked out for Bid. We find that the two cell lines are equally sensitive to killing by Pc 4-PDT, but the Bid-/- cells are significantly more resistant to killing and apoptosis induction by Pc 181-PDT than are the Bid+/+ cells. The data show that low levels of lysosomal photodamage are not alone lethal and that a specific defect in a factor required for apoptosis can severely compromise cell response to PDT.

Paper Details

Date Published: 3 March 2010
PDF: 5 pages
Proc. SPIE 7551, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XIX, 755103 (3 March 2010); doi: 10.1117/12.842523
Show Author Affiliations
Song-mao Chiu, Case Western Reserve Univ. (United States)
Liang-yan Xue, Case Western Reserve Univ. (United States)
Minh Lam, Case Western Reserve Univ. (United States)
Case Comprehensive Cancer Ctr., Case Western Reserve Univ. (United States)
Myriam E. Rodriguez, Case Western Reserve Univ. (United States)
Ping Zhang, Case Western Reserve Univ. (United States)
Malcolm E. Kenney, Case Western Reserve Univ. (United States)
Case Comprehensive Cancer Ctr., Case Western Reserve Univ. (United States)
Anna-Liisa Nieminen, Medical Univ. of South Carolina (United States)
Hollings Cancer Ctr., Medical Univ. of South Carolina (United States)
Nancy L. Oleinick, Case Western Reserve Univ. (United States)
Case Comprehensive Cancer Ctr., Case Western Reserve Univ. (United States)


Published in SPIE Proceedings Vol. 7551:
Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XIX
David H. Kessel, Editor(s)

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