Abstract
When photodynamic therapy is directed against sub-cellular sites that include mitochondria, the anti-apoptotic protein Bcl-2, lysosomes or the endoplasmic reticulum, there is generally an apoptotic response leading to cell death. We previously reported that the targeting of the plasma membrane by photosensitizing agents led to either a marked delay or inhibition of apoptosis, even if other sub-cellular sites were also targeted for photodamage. Preliminary studies indicated that this result was associated with photodamage to caspase-3, a major element of the ‘execution’ phase of apoptosis. We describe here a mechanism for apoptosis inhibition resulting from localization of photosensitizers from the membrane to the cytosol during irradiation, leading to selective photodamage of procaspases-9, and -3.
Similar content being viewed by others
References
T.J. Dougherty, C.J. Gomer, B.W. Henderson, G. Jori, D. Kessel, M. Korbelik, J. Moan and Q. Peng, Photodynamic therapy, J. Natl. Cancer Inst., 1998, 90, 889–905.
M.L. Agarwal, M.E. Clay, E.J. Harvey, H.H. Evans, A.R. Antunez and N.L. Oleinick, Photodynamic therapy induces rapid cell death by apoptosis in L5178Y mouse lymphoma cells, Cancer Res., 1991, 51, 5993–5996.
K.C. Zimmermann and D.R. Green, How cells die: apoptosis pathways, J Allergy Clin. Immunol, 1991, 108(4 Suppl), S99–103.
X. Liu, C.N. Kim, J. Yang, R. Jemmerson and X. Wang, Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c, Cell, 1996, 86, 147–157.
D. Kessel and Y. Luo, Photodynamic therapy: a mitochondrial inducer of apoptosis, Cell Death Differ., 1999, 6, 28–35.
H.R. Kim, Y. Luo, G. Li and D. Kessel, Enhanced apoptotic response to photodynamic therapy after bcl-2 transfection, Cancer Res., 1999, 59, 3429–3432.
D. Kessel and M. Castelli, Evidence that bcl-2 is the target of three photosensitizers that induce a rapid apoptotic response, Photochem. Photobiol., 2001, 74, 318–322.
L.Y. Xue, S.M. Chiu and N.L. Oleinick, Photochemical destruction of the Bcl-2 oncoprotein during photodynamic therapy with the phthalocyanine photosensitizer Pc 4, Oncogene, 2001, 20, 3420–3427.
A. Gross, J.M. McDonnell and S.J. Korsmeyer, Bcl-2 family members and the mitochondria in apoptosis, Genes Dev., 1999, 13, 1899–1911.
D. Kessel, Y. Luo, Y. Deng and C.K. Chang, The role of subcellular localization in initiation of apoptosis by photodynamic therapy, Photochem. Photobiol, 1997, 65, 422–426.
S.R. Wood, J.A. Holroyd and S.B. Brown, The subcellular localization of Zn(ǼǼ) phthalocyanines and their redistribution on exposure to light, Photochem. Photobiol., 1997, 65, 397–402.
K. Berg, K. Madslien, J.C. Bommer, R. Oftebro, J.W. Winkelman and J. Moan, Light induced relocalization of sulfonated mesotetraphenylporphines in NHIK 3025 cells and effects of dose fractionation, Photochem. Photobiol., 1991, 53, 203–210.
D. Kessel, K. Woodburn, B.W. Henderson and C.K. Chang, Sites of photodamage in vivo and in vitro by a cationic porphyrin, Photochem. Photobiol., 1995, 62, 875–881.
D. Kessel, Death mechanisms in photodynamic therapy, in Photobiology for the 21st Century, ed. T. Coohill Valdenmar Publ. Co., Overland Park, KS, 2002, in press.
D. Kessel and Y. Luo, Intracellular sites of photodamage as a factor in apoptotic cell death, J. Porphyrins Phthalocyanines., 2001, 5, 181–184.
S.X. Cai, H.Z. Zhang, J. Guastella, J. Drewe, W. Yang W and E. Weber, Design and synthesis of rhodamine 110 derivative and caspase-3 substrate for enzyme and cell-based fluorescent assay, Bioorg. Med. Chem. Lett., 2001, 11, 39–42.
Acknowledgements
Anne Marie Santiago and Brendan Leeson provided excellent technical assistance. This work was supported in part by grants CA23378 and 92618 from the NCI, NIH.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Kessel, D. Relocalization of cationic porphyrins during photodynamic therapy. Photochem Photobiol Sci 1, 837–840 (2002). https://doi.org/10.1039/b206046a
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1039/b206046a