Sensitivity of cancer cells to truncated diphtheria toxin.
Diphtheria toxin (DT) has been utilized as a prospective anti-cancer agent for the targeted delivery of cytotoxic therapy to otherwise untreatable neoplasia. DT is an extremely potent toxin for which the entry of a single molecule into a cell can be lethal. DT has been targeted to cancer cells by de...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2010-05-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC2864767?pdf=render |
| _version_ | 1811221795846488064 |
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| author | Yi Zhang Wendy Schulte Desmond Pink Kyle Phipps Andries Zijlstra John D Lewis David Morton Waisman |
| author_facet | Yi Zhang Wendy Schulte Desmond Pink Kyle Phipps Andries Zijlstra John D Lewis David Morton Waisman |
| author_sort | Yi Zhang |
| collection | DOAJ |
| description | Diphtheria toxin (DT) has been utilized as a prospective anti-cancer agent for the targeted delivery of cytotoxic therapy to otherwise untreatable neoplasia. DT is an extremely potent toxin for which the entry of a single molecule into a cell can be lethal. DT has been targeted to cancer cells by deleting the cell receptor-binding domain and combining the remaining catalytic portion with targeting proteins that selectively bind to the surface of cancer cells. It has been assumed that "receptorless" DT cannot bind to and kill cells. In the present study, we report that "receptorless" recombinant DT385 is in fact cytotoxic to a variety of cancer cell lines.In vitro cytotoxicity of DT385 was measured by cell proliferation, cell staining and apoptosis assays. For in vivo studies, the chick chorioallantoic membrane (CAM) system was used to evaluate the effect of DT385 on angiogenesis. The CAM and mouse model system was used to evaluate the effect of DT385 on HEp3 and Lewis lung carcinoma (LLC) tumor growth, respectively.Of 18 human cancer cell lines tested, 15 were affected by DT385 with IC(50) ranging from 0.12-2.8 microM. Furthermore, high concentrations of DT385 failed to affect growth arrested cells. The cellular toxicity of DT385 was due to the inhibition of protein synthesis and induction of apoptosis. In vivo, DT385 diminished angiogenesis and decreased tumor growth in the CAM system, and inhibited the subcutaneous growth of LLC tumors in mice.DT385 possesses anti-angiogenic and anti-tumor activity and may have potential as a therapeutic agent. |
| first_indexed | 2024-04-12T08:05:27Z |
| format | Article |
| id | doaj.art-2a9594ae957f4557936a428a12886d37 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-04-12T08:05:27Z |
| publishDate | 2010-05-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-2a9594ae957f4557936a428a12886d372022-12-22T03:41:10ZengPublic Library of Science (PLoS)PLoS ONE1932-62032010-05-0155e1049810.1371/journal.pone.0010498Sensitivity of cancer cells to truncated diphtheria toxin.Yi ZhangWendy SchulteDesmond PinkKyle PhippsAndries ZijlstraJohn D LewisDavid Morton WaismanDiphtheria toxin (DT) has been utilized as a prospective anti-cancer agent for the targeted delivery of cytotoxic therapy to otherwise untreatable neoplasia. DT is an extremely potent toxin for which the entry of a single molecule into a cell can be lethal. DT has been targeted to cancer cells by deleting the cell receptor-binding domain and combining the remaining catalytic portion with targeting proteins that selectively bind to the surface of cancer cells. It has been assumed that "receptorless" DT cannot bind to and kill cells. In the present study, we report that "receptorless" recombinant DT385 is in fact cytotoxic to a variety of cancer cell lines.In vitro cytotoxicity of DT385 was measured by cell proliferation, cell staining and apoptosis assays. For in vivo studies, the chick chorioallantoic membrane (CAM) system was used to evaluate the effect of DT385 on angiogenesis. The CAM and mouse model system was used to evaluate the effect of DT385 on HEp3 and Lewis lung carcinoma (LLC) tumor growth, respectively.Of 18 human cancer cell lines tested, 15 were affected by DT385 with IC(50) ranging from 0.12-2.8 microM. Furthermore, high concentrations of DT385 failed to affect growth arrested cells. The cellular toxicity of DT385 was due to the inhibition of protein synthesis and induction of apoptosis. In vivo, DT385 diminished angiogenesis and decreased tumor growth in the CAM system, and inhibited the subcutaneous growth of LLC tumors in mice.DT385 possesses anti-angiogenic and anti-tumor activity and may have potential as a therapeutic agent.http://europepmc.org/articles/PMC2864767?pdf=render |
| spellingShingle | Yi Zhang Wendy Schulte Desmond Pink Kyle Phipps Andries Zijlstra John D Lewis David Morton Waisman Sensitivity of cancer cells to truncated diphtheria toxin. PLoS ONE |
| title | Sensitivity of cancer cells to truncated diphtheria toxin. |
| title_full | Sensitivity of cancer cells to truncated diphtheria toxin. |
| title_fullStr | Sensitivity of cancer cells to truncated diphtheria toxin. |
| title_full_unstemmed | Sensitivity of cancer cells to truncated diphtheria toxin. |
| title_short | Sensitivity of cancer cells to truncated diphtheria toxin. |
| title_sort | sensitivity of cancer cells to truncated diphtheria toxin |
| url | http://europepmc.org/articles/PMC2864767?pdf=render |
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