Ionizing radiation enhances the therapeutic potential of TRAIL in prostate cancer in vitro and in vivo: Intracellular mechanisms
Background We assessed the influence of sequential treatment of ionizing radiation followed by tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) on intracellular mechanisms of apoptosis of prostate tumor cells in vitro and in vivo. Methods Prostate normal and cancer cells were ex...
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| Veröffentlicht in: | The Prostate 2004-09, Vol.61 (1), p.35-49 |
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| creator | Shankar, Sharmila Singh, Thiyam Ramsing Srivastava, Rakesh K. |
| description | Background
We assessed the influence of sequential treatment of ionizing radiation followed by tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) on intracellular mechanisms of apoptosis of prostate tumor cells in vitro and in vivo.
Methods
Prostate normal and cancer cells were exposed to irradiation and TRAIL. Four‐ to 6‐week‐old athymic nude mice were injected s.c. with PC‐3 tumor cells. Tumor bearing mice were exposed to irradiation and TRAIL, either alone or in combination (TRAIL after 24 hr of irradiation), and tumor growth, apoptosis, and survival of mice were examined. Expressions of death receptors, Bcl‐2 family members, and caspase were measured by Western blotting, ELISA, and ribonuclease protection assay; tumor cellularity was assessed by H&E staining; inhibition of p53 was performed by RNA interference (RNAi) technology, and apoptosis was measured by annexin V/propidium iodide staining, and terminal deoxynucleotidyltransferase‐mediated nick end labeling assay.
Results
Irradiation significantly augmented TRAIL‐induced apoptosis in prostate cancer cells through upregulation of DR5, Bax, and Bak, and induction of caspase activation. Dominant negative FADD and p53 siRNA inhibited the synergistic interaction between irradiation and TRAIL. The pretreatment of cells with irradiation followed by TRAIL significantly enhanced more apoptosis than single agent alone or concurrent treatment. Furthermore, irradiation sensitized TRAIL‐resistant LNCaP cells to undergo apoptosis. The sequential treatment of xenografted mice with irradiation followed by TRAIL‐induced apoptosis through activation of caspase‐3, induction of Bax and Bak, and inhibition of Bcl‐2, and completely eradicated the established tumors with enhanced survival of nude mice.
Conclusion
The sequential treatment with irradiation followed by TRAIL can be used as a viable option to enhance the therapeutic potential of TRAIL in prostate cancer. © 2004 Wiley‐Liss, Inc. |
| doi_str_mv | 10.1002/pros.20069 |
| format | Article |
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We assessed the influence of sequential treatment of ionizing radiation followed by tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) on intracellular mechanisms of apoptosis of prostate tumor cells in vitro and in vivo.
Methods
Prostate normal and cancer cells were exposed to irradiation and TRAIL. Four‐ to 6‐week‐old athymic nude mice were injected s.c. with PC‐3 tumor cells. Tumor bearing mice were exposed to irradiation and TRAIL, either alone or in combination (TRAIL after 24 hr of irradiation), and tumor growth, apoptosis, and survival of mice were examined. Expressions of death receptors, Bcl‐2 family members, and caspase were measured by Western blotting, ELISA, and ribonuclease protection assay; tumor cellularity was assessed by H&E staining; inhibition of p53 was performed by RNA interference (RNAi) technology, and apoptosis was measured by annexin V/propidium iodide staining, and terminal deoxynucleotidyltransferase‐mediated nick end labeling assay.
Results
Irradiation significantly augmented TRAIL‐induced apoptosis in prostate cancer cells through upregulation of DR5, Bax, and Bak, and induction of caspase activation. Dominant negative FADD and p53 siRNA inhibited the synergistic interaction between irradiation and TRAIL. The pretreatment of cells with irradiation followed by TRAIL significantly enhanced more apoptosis than single agent alone or concurrent treatment. Furthermore, irradiation sensitized TRAIL‐resistant LNCaP cells to undergo apoptosis. The sequential treatment of xenografted mice with irradiation followed by TRAIL‐induced apoptosis through activation of caspase‐3, induction of Bax and Bak, and inhibition of Bcl‐2, and completely eradicated the established tumors with enhanced survival of nude mice.
Conclusion
The sequential treatment with irradiation followed by TRAIL can be used as a viable option to enhance the therapeutic potential of TRAIL in prostate cancer. © 2004 Wiley‐Liss, Inc.</description><identifier>ISSN: 0270-4137</identifier><identifier>EISSN: 1097-0045</identifier><identifier>DOI: 10.1002/pros.20069</identifier><identifier>PMID: 15287092</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Animals ; apoptosis ; Apoptosis - drug effects ; Apoptosis - radiation effects ; Apoptosis Regulatory Proteins ; Arabidopsis Proteins - metabolism ; Bak ; Bax ; Bcl-2 ; bcl-2 Homologous Antagonist-Killer Protein ; Caspases - metabolism ; Cell Line, Tumor ; Combined Modality Therapy ; death receptors ; Fatty Acid Desaturases - metabolism ; Genes, bcl-2 ; irradiation ; Male ; Membrane Glycoproteins - pharmacology ; Membrane Proteins - metabolism ; Methyl Ethers - metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; p53 ; prostate cancer ; Prostatic Neoplasms - drug therapy ; Prostatic Neoplasms - metabolism ; Prostatic Neoplasms - pathology ; Prostatic Neoplasms - radiotherapy ; Proto-Oncogene Proteins c-bcl-2 - metabolism ; Random Allocation ; Receptors, TNF-Related Apoptosis-Inducing Ligand ; Receptors, Tumor Necrosis Factor - metabolism ; TNF-Related Apoptosis-Inducing Ligand ; TRAIL ; Tumor Necrosis Factor-alpha - pharmacology ; Tumor Suppressor Protein p53 - metabolism</subject><ispartof>The Prostate, 2004-09, Vol.61 (1), p.35-49</ispartof><rights>Copyright © 2004 Wiley‐Liss, Inc.</rights><rights>Copyright 2004 Wiley-Liss, Inc.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4299-abad83f9a1df19f68c6512f4341bfc3e12e6d7d3d720e585e806fccab15143d13</citedby><cites>FETCH-LOGICAL-c4299-abad83f9a1df19f68c6512f4341bfc3e12e6d7d3d720e585e806fccab15143d13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fpros.20069$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fpros.20069$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15287092$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shankar, Sharmila</creatorcontrib><creatorcontrib>Singh, Thiyam Ramsing</creatorcontrib><creatorcontrib>Srivastava, Rakesh K.</creatorcontrib><title>Ionizing radiation enhances the therapeutic potential of TRAIL in prostate cancer in vitro and in vivo: Intracellular mechanisms</title><title>The Prostate</title><addtitle>Prostate</addtitle><description>Background
We assessed the influence of sequential treatment of ionizing radiation followed by tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) on intracellular mechanisms of apoptosis of prostate tumor cells in vitro and in vivo.
Methods
Prostate normal and cancer cells were exposed to irradiation and TRAIL. Four‐ to 6‐week‐old athymic nude mice were injected s.c. with PC‐3 tumor cells. Tumor bearing mice were exposed to irradiation and TRAIL, either alone or in combination (TRAIL after 24 hr of irradiation), and tumor growth, apoptosis, and survival of mice were examined. Expressions of death receptors, Bcl‐2 family members, and caspase were measured by Western blotting, ELISA, and ribonuclease protection assay; tumor cellularity was assessed by H&E staining; inhibition of p53 was performed by RNA interference (RNAi) technology, and apoptosis was measured by annexin V/propidium iodide staining, and terminal deoxynucleotidyltransferase‐mediated nick end labeling assay.
Results
Irradiation significantly augmented TRAIL‐induced apoptosis in prostate cancer cells through upregulation of DR5, Bax, and Bak, and induction of caspase activation. Dominant negative FADD and p53 siRNA inhibited the synergistic interaction between irradiation and TRAIL. The pretreatment of cells with irradiation followed by TRAIL significantly enhanced more apoptosis than single agent alone or concurrent treatment. Furthermore, irradiation sensitized TRAIL‐resistant LNCaP cells to undergo apoptosis. The sequential treatment of xenografted mice with irradiation followed by TRAIL‐induced apoptosis through activation of caspase‐3, induction of Bax and Bak, and inhibition of Bcl‐2, and completely eradicated the established tumors with enhanced survival of nude mice.
Conclusion
The sequential treatment with irradiation followed by TRAIL can be used as a viable option to enhance the therapeutic potential of TRAIL in prostate cancer. © 2004 Wiley‐Liss, Inc.</description><subject>Animals</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Apoptosis - radiation effects</subject><subject>Apoptosis Regulatory Proteins</subject><subject>Arabidopsis Proteins - metabolism</subject><subject>Bak</subject><subject>Bax</subject><subject>Bcl-2</subject><subject>bcl-2 Homologous Antagonist-Killer Protein</subject><subject>Caspases - metabolism</subject><subject>Cell Line, Tumor</subject><subject>Combined Modality Therapy</subject><subject>death receptors</subject><subject>Fatty Acid Desaturases - metabolism</subject><subject>Genes, bcl-2</subject><subject>irradiation</subject><subject>Male</subject><subject>Membrane Glycoproteins - pharmacology</subject><subject>Membrane Proteins - metabolism</subject><subject>Methyl Ethers - metabolism</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>p53</subject><subject>prostate cancer</subject><subject>Prostatic Neoplasms - drug therapy</subject><subject>Prostatic Neoplasms - metabolism</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Prostatic Neoplasms - radiotherapy</subject><subject>Proto-Oncogene Proteins c-bcl-2 - metabolism</subject><subject>Random Allocation</subject><subject>Receptors, TNF-Related Apoptosis-Inducing Ligand</subject><subject>Receptors, Tumor Necrosis Factor - metabolism</subject><subject>TNF-Related Apoptosis-Inducing Ligand</subject><subject>TRAIL</subject><subject>Tumor Necrosis Factor-alpha - pharmacology</subject><subject>Tumor Suppressor Protein p53 - metabolism</subject><issn>0270-4137</issn><issn>1097-0045</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kE9v1DAQxS0EokvLhQ-AfOKAlOI_iZ1wq1pYVlraqhTBzfLaY2pInK3tFMqpH70JWeDWgzXy6PfezDyEXlBySAlhb7axT4eMENE8QgtKGlkQUlaP0YIwSYqScrmHnqX0nZARJ-wp2qMVqyVp2ALdrfrgf_vwDUdtvc6-DxjClQ4GEs5XML2otzBkb_C2zxCy1y3uHb68OFqtsQ94Gp91BmwmVZxaNz7HHutg589N_xavQo7aQNsOrY64AzPO8KlLB-iJ022C57u6jz6_f3d5_KFYny1Xx0frwpSsaQq90bbmrtHUOto4URtRUeZKXtKNMxwoA2Gl5VYyAlVdQU2EM0ZvaEVLbinfR69m33Hd6wFSVp1P0z46QD8kJYQU5Wg5gq9n0Ix3pQhObaPvdLxVlKgpbzUdrP7kPcIvd67DpgP7H90FPAJ0Bn76Fm4fsFLnF2ef_poWs8anDL_-aXT8oYTkslJfTpdq-fX89GN5QtUJvwdB35zO</recordid><startdate>20040915</startdate><enddate>20040915</enddate><creator>Shankar, Sharmila</creator><creator>Singh, Thiyam Ramsing</creator><creator>Srivastava, Rakesh K.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><scope>BSCLL</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope></search><sort><creationdate>20040915</creationdate><title>Ionizing radiation enhances the therapeutic potential of TRAIL in prostate cancer in vitro and in vivo: Intracellular mechanisms</title><author>Shankar, Sharmila ; Singh, Thiyam Ramsing ; Srivastava, Rakesh K.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4299-abad83f9a1df19f68c6512f4341bfc3e12e6d7d3d720e585e806fccab15143d13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>Animals</topic><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Apoptosis - radiation effects</topic><topic>Apoptosis Regulatory Proteins</topic><topic>Arabidopsis Proteins - metabolism</topic><topic>Bak</topic><topic>Bax</topic><topic>Bcl-2</topic><topic>bcl-2 Homologous Antagonist-Killer Protein</topic><topic>Caspases - metabolism</topic><topic>Cell Line, Tumor</topic><topic>Combined Modality Therapy</topic><topic>death receptors</topic><topic>Fatty Acid Desaturases - metabolism</topic><topic>Genes, bcl-2</topic><topic>irradiation</topic><topic>Male</topic><topic>Membrane Glycoproteins - pharmacology</topic><topic>Membrane Proteins - metabolism</topic><topic>Methyl Ethers - metabolism</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>p53</topic><topic>prostate cancer</topic><topic>Prostatic Neoplasms - drug therapy</topic><topic>Prostatic Neoplasms - metabolism</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Prostatic Neoplasms - radiotherapy</topic><topic>Proto-Oncogene Proteins c-bcl-2 - metabolism</topic><topic>Random Allocation</topic><topic>Receptors, TNF-Related Apoptosis-Inducing Ligand</topic><topic>Receptors, Tumor Necrosis Factor - metabolism</topic><topic>TNF-Related Apoptosis-Inducing Ligand</topic><topic>TRAIL</topic><topic>Tumor Necrosis Factor-alpha - pharmacology</topic><topic>Tumor Suppressor Protein p53 - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Shankar, Sharmila</creatorcontrib><creatorcontrib>Singh, Thiyam Ramsing</creatorcontrib><creatorcontrib>Srivastava, Rakesh K.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>The Prostate</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Shankar, Sharmila</au><au>Singh, Thiyam Ramsing</au><au>Srivastava, Rakesh K.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ionizing radiation enhances the therapeutic potential of TRAIL in prostate cancer in vitro and in vivo: Intracellular mechanisms</atitle><jtitle>The Prostate</jtitle><addtitle>Prostate</addtitle><date>2004-09-15</date><risdate>2004</risdate><volume>61</volume><issue>1</issue><spage>35</spage><epage>49</epage><pages>35-49</pages><issn>0270-4137</issn><eissn>1097-0045</eissn><abstract>Background
We assessed the influence of sequential treatment of ionizing radiation followed by tumor necrosis factor (TNF)‐related apoptosis‐inducing ligand (TRAIL) on intracellular mechanisms of apoptosis of prostate tumor cells in vitro and in vivo.
Methods
Prostate normal and cancer cells were exposed to irradiation and TRAIL. Four‐ to 6‐week‐old athymic nude mice were injected s.c. with PC‐3 tumor cells. Tumor bearing mice were exposed to irradiation and TRAIL, either alone or in combination (TRAIL after 24 hr of irradiation), and tumor growth, apoptosis, and survival of mice were examined. Expressions of death receptors, Bcl‐2 family members, and caspase were measured by Western blotting, ELISA, and ribonuclease protection assay; tumor cellularity was assessed by H&E staining; inhibition of p53 was performed by RNA interference (RNAi) technology, and apoptosis was measured by annexin V/propidium iodide staining, and terminal deoxynucleotidyltransferase‐mediated nick end labeling assay.
Results
Irradiation significantly augmented TRAIL‐induced apoptosis in prostate cancer cells through upregulation of DR5, Bax, and Bak, and induction of caspase activation. Dominant negative FADD and p53 siRNA inhibited the synergistic interaction between irradiation and TRAIL. The pretreatment of cells with irradiation followed by TRAIL significantly enhanced more apoptosis than single agent alone or concurrent treatment. Furthermore, irradiation sensitized TRAIL‐resistant LNCaP cells to undergo apoptosis. The sequential treatment of xenografted mice with irradiation followed by TRAIL‐induced apoptosis through activation of caspase‐3, induction of Bax and Bak, and inhibition of Bcl‐2, and completely eradicated the established tumors with enhanced survival of nude mice.
Conclusion
The sequential treatment with irradiation followed by TRAIL can be used as a viable option to enhance the therapeutic potential of TRAIL in prostate cancer. © 2004 Wiley‐Liss, Inc.</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>15287092</pmid><doi>10.1002/pros.20069</doi><tpages>15</tpages></addata></record> |
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| subjects | Animals apoptosis Apoptosis - drug effects Apoptosis - radiation effects Apoptosis Regulatory Proteins Arabidopsis Proteins - metabolism Bak Bax Bcl-2 bcl-2 Homologous Antagonist-Killer Protein Caspases - metabolism Cell Line, Tumor Combined Modality Therapy death receptors Fatty Acid Desaturases - metabolism Genes, bcl-2 irradiation Male Membrane Glycoproteins - pharmacology Membrane Proteins - metabolism Methyl Ethers - metabolism Mice Mice, Inbred BALB C Mice, Nude p53 prostate cancer Prostatic Neoplasms - drug therapy Prostatic Neoplasms - metabolism Prostatic Neoplasms - pathology Prostatic Neoplasms - radiotherapy Proto-Oncogene Proteins c-bcl-2 - metabolism Random Allocation Receptors, TNF-Related Apoptosis-Inducing Ligand Receptors, Tumor Necrosis Factor - metabolism TNF-Related Apoptosis-Inducing Ligand TRAIL Tumor Necrosis Factor-alpha - pharmacology Tumor Suppressor Protein p53 - metabolism |
| title | Ionizing radiation enhances the therapeutic potential of TRAIL in prostate cancer in vitro and in vivo: Intracellular mechanisms |
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