Photodynamic therapy-induced death of HCT 116 cells: Apoptosis with or without Bax expression.
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.
Chiu
S-M
SM
Department of Radiation Oncology and The Case Comprehensive Cancer Center, School of Medicine, Case Western Reserve University, Cleveland, OH 44106, USA.
Xue
L-Y
LY
Azizuddin
K
K
Oleinick
N L
NL
D053148:Caspase 3 / Q000378:metabolism; D016923:Cell Death; D045304:Cytochromes c / Q000378:metabolism; D045325:HCT116 Cells; D006801:Humans; D053078:Membrane Potential, Mitochondrial; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism; D010778:Photochemotherapy; D011487:Protein Conformation; D051028:bcl-2-Associated X Protein / Q000737:chemistry / Q000378:metabolism*
D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; D053148:Caspase 3