Alteration of caspase-3 (CPP32/Yama/apopain) in wild-type MCF-7, breast cancer cells.

Kurokawa, Hitoshi; Nishio, K; Fukumoto, Hiroki; Tomonari, Akira; Suzuki, Tise; Saijo, Nagahiro

doi:10.3892/or.6.1.33

Cited by 89 publications

(101 citation statements)

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“…We and others (Fromigue et al, 2000;Senaratne et al, 2000;Jagdev et al, 2001) have demonstrated that N-BPs are capable of inducing loss of cell viability and DNA fragmentation in MCF-7 cells which are caspase-3 null (Kurokawa et al, 1999). However, our present study illustrates that in MCF-7 cells stably transfected with caspase-3, ZOL is capable of activating this cell-death protease.…”

Section: Discussioncontrasting

confidence: 71%

“…Both pro-caspase-3 and its cleaved products were absent from Experimental Therapeutics extracts of MCF-7 cells either untreated (not shown) or treated with TNF-a 12 ng ml 71 for 24 h ( Figure 3A). MCF-7 cells do not express caspase-3, but are still induced to undergo apoptosis by a number of agents (Kurokawa et al, 1999) suggesting that cell death could be associated with activation of another, as yet unidentified caspase in these cells. To determine whether N-BPs can modulate caspase-3 in these cells, we assessed effects of ZOL on a transfected clone of MCF-7 cells stably expressing caspase-3.…”

Section: Zol Treatment Induces Activation Of Caspasementioning

confidence: 99%

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The bisphosphonate zoledronic acid impairs membrane localisation and induces cytochrome c release in breast cancer cells

Mansi

2002

Br J Cancer

128

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Bisphosphonates are well established in the management of cancer-induced bone disease. Recent studies have indicated that these compounds have direct inhibitory effects on cultured human breast cancer cells. Nitrogen-containing bisphosphonates including zoledronic acid have been shown to induce apoptosis associated with PARP cleavage and DNA fragmentation. The aim of this study was to identify the signalling pathways involved. Forced expression of the anti-apoptotic protein bcl-2 attenuated bisphosphonate-induced loss of cell viability and induction of DNA fragmentation in MDA-MB-231 cells. Zoledronic acid-mediated apoptosis was associated with a time and dose-related release of mitochondrial cytochrome c into the cytosol in two cell lines. Rescue of cells by preincubation with a caspase-3 selective inhibitor and demonstration of procaspase-3 cleavage products by immunoblotting suggests that at least one of the caspases activated in response to zoledronic acid treatment is caspase-3. In both MDA-MB-231 and MCF-7 breast cancer cells, zoledronic acid impaired membrane localisation of Ras indicating reduced prenylation of this protein. These observations demonstrate that zoledronic acidmediated apoptosis is associated with cytochrome c release and consequent caspase activation. This process may be initiated by inhibition of the enzymes in the mevalonate pathway leading to impaired prenylation of key intracellular proteins including Ras.

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Section: Discussioncontrasting

confidence: 71%

Section: Zol Treatment Induces Activation Of Caspasementioning

confidence: 99%

The bisphosphonate zoledronic acid impairs membrane localisation and induces cytochrome c release in breast cancer cells

Mansi

2002

Br J Cancer

128

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“…This conjecture is supported by our previous experience with introduction of wild-type p53 using adenoviral vectors (adv.wtp53), whereby cancer cells with mutant or absent p53 are far more sensitive to this therapeutic strategy than tumors with retained p53 function. 20 Another possibility, of course, could relate to the fact that MCF-7 cells lack functional caspase-3, 39 resulting in greater intrinsic resistance to apoptosis, regardless of the insult.…”

Section: Discussionmentioning

confidence: 99%

Kinase-dead PKB gene therapy combined with hyperthermia for human breast cancer

Szmitko

Brade

et al. 2003

Cancer Gene Ther

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We have previously demonstrated that protein kinase B (PKB) is a mediator of heat-induced apoptosis for human breast cancer cells. To investigate the therapeutic potential of abrogating the function of this important survival protein, a novel replication-deficient adenovirus was constructed, wherein a mutant, kinase-inactive PKB gene (AAA) was inserted downstream of the CMV promoter. Two human breast cancer cell lines, MCF-7 and MDA-468, were treated, along with the MCF-10 serving as a ''normal'' mammary epithelial comparator. Apoptosis was increased with adv.AAA (25 PFU/cell) infection alone, but was significantly enhanced with the addition of heat exposure. Differential survival was observed with the MDA-468 cancer cells being more sensitive than the MCF-7 cells. The MCF-10 cells, in contrast, were most resistant to these treatments. Results from the clonogenic assay reflected the apoptosis data, with an apparent additive interaction between adv.AAA and hyperthermia treatments, again with greater differential sensitivity of the malignant, compared to the ''normal'' mammary epithelial cells. Heat or adv.b-gal treatments led to phosphorylation of PKB and Forkhead, but this phosphorylation was reduced with adv.AAA therapy. In parallel, the combination of adv.AAA and heat treatment reduced PKB kinase activity more so than with either heat or adv.b-gal alone. In conclusion, our results demonstrate that inhibition of the PKB-dependent survival pathway will promote apoptosis and thermosensitization in malignant breast cancer cells, with relative sparing of their normal counterpart, suggesting that a therapeutic gain could be achievable using this therapeutic strategy.

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“…This indicates that N5-induced apoptosis is independent of p53. MCF-7 cells, conversely, lack functional caspase-3, 13 yet these cells are sensitive to N5-mediated apoptosis. Hence, caspase-3 is not required for N5-induced apoptosis.…”

Section: Yin Hung and Goodrich: N5 Adenovirus Induces Apoptosis In mentioning

confidence: 99%

Adenovirus-mediated N5 gene transfer inhibits tumor cell proliferation by induction of apoptosis

2000

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Gene therapy designed to initiate apoptotic cell death provides a potentially effective method to treat cancer. A prerequisite for this approach is the identification of genes that function in distinct apoptotic pathways. Although apoptotic pathways initiated by receptors such as tumor necrosis factor receptor-1 are well characterized, little is known about apoptotic pathways initiated within the nucleus in response to genotoxic stress. We have demonstrated previously that the nuclear, death domain-containing protein p84N5 can induce apoptosis upon transfection into cells, suggesting that it may play a role in an apoptotic pathway initiated within the nucleus. To test the possibility that N5 could be used in the gene therapy of cancer, we have generated a recombinant adenovirus engineered to express N5 and tested the effects of viral infection on the growth and tumorigenicity of tumor cells. N5 adenovirus infection significantly reduced the proliferation and tumorigenicity of breast, ovarian, and osteosarcoma tumor cell lines. Reduced proliferation and tumorigenicity were mediated by an induction of apoptosis as indicated by DNA fragmentation in infected cells. The results suggest that the N5 cDNA is a candidate for the gene therapy of cancer. Cancer Gene Therapy (2000) 7, 985-990

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Alteration of caspase-3 (CPP32/Yama/apopain) in wild-type MCF-7, breast cancer cells.

Cited by 89 publications

References 0 publications

The bisphosphonate zoledronic acid impairs membrane localisation and induces cytochrome c release in breast cancer cells

The bisphosphonate zoledronic acid impairs membrane localisation and induces cytochrome c release in breast cancer cells

Kinase-dead PKB gene therapy combined with hyperthermia for human breast cancer

Adenovirus-mediated N5 gene transfer inhibits tumor cell proliferation by induction of apoptosis

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