Photodynamic Therapy-Induced Death of MCF-7 Human Breast Cancer Cells: A Role for Caspase-3 in the Late Steps of Apoptosis but Not for the Critical Lethal Event

Xue, Liang-yan; Chiu, Song Mao; Oleinick, Nancy L.

doi:10.1006/excr.2000.5108

Cited by 117 publications

(120 citation statements)

References 49 publications

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“…It has been demonstrated that, despite the presence of functional effector caspase 7, apoptotic response to some stimuli, including staurosporine, VP-16 38 and photodynamic therapy, 39 was delayed or diminished in this cell line. Reconstitution of caspase 3 expression enhanced apoptosis induced by staurosporine and chemotherapeutic agents.…”

Section: Discussionmentioning

confidence: 89%

Death receptor 4 (DR4) efficiently kills breast cancer cells irrespective of their sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)

Kazhdan

Marciniak

2004

Cancer Gene Ther

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and 2 South Texas Veterans Health Care System, Texas, USA.Breast cancer cells are generally resistant to induction of apoptosis by treatment with tumor necrosis factor-related apoptosisinducing ligand (TRAIL). In this study, we demonstrate that both TRAIL-sensitive and TRAIL-resistant breast cancer cell lines can be efficiently killed by overexpression of the TRAIL receptor, death receptor 4 (DR4). The extent of cell death depended on the strength of the promoter driving DR4 expression. When driven by the strong CMV promoter, expression of DR4 killed over 90% of cells in five out of six cell lines tested in the absence of exogenous TRAIL. When driven by the relatively weak tumor-specific hTERT promoter, DR4 was less effective alone, but sensitized cells to killing by TRAIL. The extent of TRAIL sensitization depended on the magnitude of hTERT promoter activity. MCF-7 cells were relatively resistant to the action of DR4. We compared expression of the genes involved in transduction and execution of the death receptor-initiated apoptotic stimuli between MCF-7 and DR4-sensitive cell lines. We confirmed that in the panel of cell lines, MCF-7 was the only line deficient in expression of caspase 3. Bcl-2 and FLIP proteins, implicated in suppression of TRAIL-induced apoptosis, were expressed at a higher level.

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Section: Discussionmentioning

confidence: 89%

Death receptor 4 (DR4) efficiently kills breast cancer cells irrespective of their sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)

Kazhdan

Marciniak

2004

Cancer Gene Ther

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“…There is strong evidence that sensitisers with an acute localisation in mitochondria promote the release of cytochrome c upon irradiation (Xue et al, 2001). This loss of cytochrome c can be lethal to cells either because of the disruption of the mitochondrial respiratory chain with the eventual reduction of cellular ATP levels or through caspase initiation with subsequent apoptotic cell death (Yow et al, 2000;Xue et al, 2001).…”

Section: Discussionmentioning

confidence: 99%

“…This loss of cytochrome c can be lethal to cells either because of the disruption of the mitochondrial respiratory chain with the eventual reduction of cellular ATP levels or through caspase initiation with subsequent apoptotic cell death (Yow et al, 2000;Xue et al, 2001). Figure 3C shows that mitochondrial-localising Rh123 and Foscan s fluorescence topographic patterns were different, indicating a poor affinity of Foscan s for these organelles.…”

Section: Discussionmentioning

confidence: 99%

Endoplasmic reticulum and Golgi apparatus are the preferential sites of Foscan® localisation in cultured tumour cells

et al. 2003

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Intracellular photosensitiser localisation significantly influences the mechanism of response to photodynamic therapy (PDT), since the primary sites of damage are closely related to the specific sensitiser distribution. Foscan s subcellular localisation in the MCF-7 human adenocarcinoma cell line has been studied by means of confocal microscopy and microspectrofluorometry. The fluorescence topographic profiles recorded after cells costained with Foscan s and organelle-specific fluorescent probes revealed that Foscan s presents low localisation in lysosomes and a weak accumulation in mitochondria. Alternatively, the Foscan s fluorescence topographic profile turned out to colocalise perfectly with that obtained for the endoplasmic reticulum (ER) and the Golgi apparatus. The patterns of fluorescence derived from confocal microscopy studies were consistent with predominant localisation of Foscan s in these organelles. Furthermore, evaluation of enzymatic activity of selected organelles immediately after laser light irradiation (650 nm) indicated the Golgi apparatus and ER as the primary damaged sites resulting from Foscan s -mediated PDT in the MCF-7 cell line. To our knowledge, this is the first study to demonstrate unambiguously that the ER and the Golgi apparatus are preferential sites of Foscan s accumulation.

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“…The responsiveness of the Bax knockdown is consistent with reports by Oleinick's group showing that absence of Bax, or of procaspase-3, did not protect cells from phototoxic effects of PDT using the phthalocyanine photosensitizer Pc 4. [3][4][5][6] Time sequence of autophagy and apoptosis A typical result after exposure of L1210 cells to an LD 90 PDT dose of CPO is shown in Fig. 5.…”

Section: Apoptotic and Cytotoxic Response To Pdtmentioning

confidence: 99%

Apoptotic and autophagic responses to Bcl-2 inhibition and photodamage

Kessel

Arroyo

2007

Photochem Photobiol Sci

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Among the cellular responses to photodamage initiated by photodynamic therapy (PDT) are autophagy and apoptosis. While autophagy is a reversible process that can be both a survival and a death pathway, apoptosis is irreversible, leading only to cell death. In this study, we followed the fate of mouse leukemia L1210 cells after photodamage to the endoplasmic reticulum (ER) using a porphycene photosensitizer, where Bcl-2 was among the PDT targets. In wild-type cells, we observed a rapid wave of autophagy, presumed to represent the recycling of some damaged organelles, followed by apoptosis. Using shRNA technology, we created a Bax knockdown line (L1210/Bax − ). In the latter cell line, we found a marked decrease in apoptosis after photodamage or pharmacologic inactivation of Bcl-2 function, but this did not affect PDT efficacy. Loss of viability was associated with a highly-vacuolated morphology consistent with autophagic cell death. Previous studies indicated pro-survival attributes of autophagy after low-dose PDT, suggesting that autophagy may be responsible for the 'shoulder' on the dose-response curve. It appears that attempts at extensive recycling of damaged organelles are associated with cell death, and that this phenomenon is amplified when apoptosis is suppressed.

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Photodynamic Therapy-Induced Death of MCF-7 Human Breast Cancer Cells: A Role for Caspase-3 in the Late Steps of Apoptosis but Not for the Critical Lethal Event

Cited by 117 publications

References 49 publications

Death receptor 4 (DR4) efficiently kills breast cancer cells irrespective of their sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)

Death receptor 4 (DR4) efficiently kills breast cancer cells irrespective of their sensitivity to tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)

Endoplasmic reticulum and Golgi apparatus are the preferential sites of Foscan® localisation in cultured tumour cells

Apoptotic and autophagic responses to Bcl-2 inhibition and photodamage

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