Photodynamic therapy-induced death of HCT 116 cells: Apoptosis with or without Bax expression |
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Authors: | S-M?Chiu L-Y?Xue K?Azizuddin Email author" target="_blank">N?L?OleinickEmail author |
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Affiliation: | (1) Department of Radiation Oncology and The Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA;(2) Department of Radiation Oncology, School of Medicine (BRB-324), Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106-4942, USA |
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Abstract: | Cell death following photodynamic therapy (PDT) with the photosensitizer Pc 4 involves the intrinsic pathway of apoptosis.
To evaluate the importance of Bax in apoptosis after PDT, we compared the PDT responses of Bax-proficient (Bax+/−) and Bax knock-out (BaxKO) HCT116 human colon cancer cells. PDT induced a slow apoptotic process in HCT Bax+/− cells following a long delay in the activation of Bax and release of cytochrome c from mitochondria. Although cytochrome c was not released from mitochondria following PDT in BaxKO cells, an alternative mechanism of caspase-dependent apoptosis
with extensive chromatin and DNA degradation was found in these cells. This alternative process was less efficient and slower
than the normal apoptotic process observed in Bax+/− cells. Early events upon PDT, such as the loss of mitochondrial membrane potential, photodamage to Bcl-2, and activation
of p38 MAP kinase, were observed in both HCT116 cell lines. In spite of differences in the efficiency and mode of apoptosis
induced by PDT in the Bax+/− and BaxKO cells, they were found to be equally sensitive to killing by PDT, as determined by loss of clonogenicity. Thus,
for Pc 4-PDT, the commitment to cell death occurs prior to and independent of Bax activation, but the process of cellular
disassembly differs in Bax-expressing vs. non-expressing cells. |
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Keywords: | apoptosis bax cell death photodynamic therapy phthalocyanine Pc 4 |
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