Molecular factors in cell (and tumor) response to photodynamic therapy: the role of Bid

Song-mao Chiu; Liang-yan Xue; Minh Lam; Myriam E. Rodriguez; Ping Zhang; Malcolm E. Kenney; Anna-Liisa Nieminen; Nancy L. Oleinick

doi:10.1117/12.842523

2 March 2010 Molecular factors in cell (and tumor) response to photodynamic therapy: the role of Bid

Song-mao Chiu, Liang-yan Xue, Minh Lam, Myriam E. Rodriguez, Ping Zhang, Malcolm E. Kenney, Anna-Liisa Nieminen, Nancy L. Oleinick

Author Affiliations +

Proceedings Volume 7551, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XIX; 755103 (2010) https://doi.org/10.1117/12.842523
Event: SPIE BiOS, 2010, San Francisco, California, United States

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.

Citation Download Citation

Song-mao Chiu, Liang-yan Xue, Minh Lam, Myriam E. Rodriguez, Ping Zhang, Malcolm E. Kenney, Anna-Liisa Nieminen, and Nancy L. Oleinick "Molecular factors in cell (and tumor) response to photodynamic therapy: the role of Bid", Proc. SPIE 7551, Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XIX, 755103 (2 March 2010); https://doi.org/10.1117/12.842523

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