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Anticancer activity of RecQL1 helicase siRNA in mouse xenograft models
Small interfering RNAs (siRNAs) are expected to have a medical application in human therapy as drugs with a high specificity for their molecular target mRNAs. RecQL1 DNA helicase in the human RecQ helicase family participates in DNA repair and recombination pathways in the cell cycle of replication....
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| Published in: | Cancer science 2008-06, Vol.99 (6), p.1227-1236 |
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| container_end_page | 1236 |
| container_issue | 6 |
| container_start_page | 1227 |
| container_title | Cancer science |
| container_volume | 99 |
| creator | Futami, Kazunobu Kumagai, Emi Makino, Hiroshi Sato, Ayumi Takagi, Motoki Shimamoto, Akira Furuichi, Yasuhiro |
| description | Small interfering RNAs (siRNAs) are expected to have a medical application in human therapy as drugs with a high specificity for their molecular target mRNAs. RecQL1 DNA helicase in the human RecQ helicase family participates in DNA repair and recombination pathways in the cell cycle of replication. Silencing the RecQL1 expression by RecQL1‐siRNA induces mitotic death in vitro specifically in growing cancer cells. By contrast, the same RecQL1 silencing does not affect the growth of normal cells, emphasizing that RecQL1 helicase is an ideal molecular target for cancer therapy. In this study, we show that local and systemic administration of RecQL1‐siRNA mixed with polyethyleneimine polymer or cationic liposomes prevented cancer cell proliferation in vivo in mouse models of cancer without noticeable adverse effects. The results indicate that RecQL1‐siRNA in a complex with a cationic polymer is a very promising anticancer drug candidate, and that in particular, RecQL1‐siRNA formulated with a cationic liposome has an enormous potential to be used by intravenous injection for therapy specific for liver cancers, including metastasized cancers from the colon and pancreas. (Cancer Sci 2008; 99: 1227–1236) |
| doi_str_mv | 10.1111/j.1349-7006.2008.00794.x |
| format | article |
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RecQL1 DNA helicase in the human RecQ helicase family participates in DNA repair and recombination pathways in the cell cycle of replication. Silencing the RecQL1 expression by RecQL1‐siRNA induces mitotic death in vitro specifically in growing cancer cells. By contrast, the same RecQL1 silencing does not affect the growth of normal cells, emphasizing that RecQL1 helicase is an ideal molecular target for cancer therapy. In this study, we show that local and systemic administration of RecQL1‐siRNA mixed with polyethyleneimine polymer or cationic liposomes prevented cancer cell proliferation in vivo in mouse models of cancer without noticeable adverse effects. The results indicate that RecQL1‐siRNA in a complex with a cationic polymer is a very promising anticancer drug candidate, and that in particular, RecQL1‐siRNA formulated with a cationic liposome has an enormous potential to be used by intravenous injection for therapy specific for liver cancers, including metastasized cancers from the colon and pancreas. 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RecQL1 DNA helicase in the human RecQ helicase family participates in DNA repair and recombination pathways in the cell cycle of replication. Silencing the RecQL1 expression by RecQL1‐siRNA induces mitotic death in vitro specifically in growing cancer cells. By contrast, the same RecQL1 silencing does not affect the growth of normal cells, emphasizing that RecQL1 helicase is an ideal molecular target for cancer therapy. In this study, we show that local and systemic administration of RecQL1‐siRNA mixed with polyethyleneimine polymer or cationic liposomes prevented cancer cell proliferation in vivo in mouse models of cancer without noticeable adverse effects. The results indicate that RecQL1‐siRNA in a complex with a cationic polymer is a very promising anticancer drug candidate, and that in particular, RecQL1‐siRNA formulated with a cationic liposome has an enormous potential to be used by intravenous injection for therapy specific for liver cancers, including metastasized cancers from the colon and pancreas. (Cancer Sci 2008; 99: 1227–1236)</description><subject>Animals</subject><subject>Biological and medical sciences</subject><subject>Carcinoma, Hepatocellular - enzymology</subject><subject>Carcinoma, Hepatocellular - genetics</subject><subject>Carcinoma, Hepatocellular - therapy</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>Colorectal Neoplasms - enzymology</subject><subject>Colorectal Neoplasms - genetics</subject><subject>Colorectal Neoplasms - therapy</subject><subject>Flow Cytometry</subject><subject>Humans</subject><subject>Immunoenzyme Techniques</subject><subject>Liposomes</subject><subject>Liver Neoplasms, Experimental - genetics</subject><subject>Liver Neoplasms, Experimental - secondary</subject><subject>Liver Neoplasms, Experimental - therapy</subject><subject>Lung Neoplasms - enzymology</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - therapy</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Neoplasms, Experimental - drug therapy</subject><subject>Neoplasms, Experimental - enzymology</subject><subject>Neoplasms, Experimental - genetics</subject><subject>Original /Report</subject><subject>Pancreatic Neoplasms - enzymology</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - therapy</subject><subject>Polyethyleneimine - chemistry</subject><subject>RecQ Helicases - antagonists & inhibitors</subject><subject>RecQ Helicases - genetics</subject><subject>RecQ Helicases - metabolism</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>RNA, Messenger - genetics</subject><subject>RNA, Messenger - metabolism</subject><subject>RNA, Small Interfering - pharmacology</subject><subject>Tumors</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1347-9032</issn><issn>1349-7006</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><recordid>eNqNkU1vEzEQhq0KREvLX6j2Arfdjj9iryUkFEUtrRSBaOFseZ1x62izW-xNSf493iZK4QS-eEbzzOdLSEGhovldLCvKhS4VgKwYQF0BKC2qzRE5OQRePduq1MDZMXmb0hKAS6HFG3JMa8GYEuqEXE27ITjbOYyFdUN4CsO26H1xi-7bnBYP2OZowiKF2y_TInTFql9nd4Ndfx-tH7K_wDadkdfetgnf7f9T8uPq8vvsupx__Xwzm85LJ4GJUnhdK7VgqKHxtNFeKU1lzRqhnfM4UVwBk5IjZRqFdI1qUDqnGUWYcFnzU_JpV_dx3axw4bAbom3NYwwrG7emt8H8HenCg7nvn0y-2kTLCeQKH_YVYv9zjWkwq5Actq3tMK9mFCjBGVf_BBkIrjTXGax3oIt9ShH9YRwKY19qlmZUxYyqmFEu8yyX2eTU8z_XeUnc65OB93vAJmdbH7NSIR04BrzWrB7v8nHH_Qotbv97ADOb3mWD_wbYWK--</recordid><startdate>200806</startdate><enddate>200806</enddate><creator>Futami, Kazunobu</creator><creator>Kumagai, Emi</creator><creator>Makino, Hiroshi</creator><creator>Sato, Ayumi</creator><creator>Takagi, Motoki</creator><creator>Shimamoto, Akira</creator><creator>Furuichi, Yasuhiro</creator><general>Blackwell Publishing Asia</general><general>Blackwell</general><scope>IQODW</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>7QO</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200806</creationdate><title>Anticancer activity of RecQL1 helicase siRNA in mouse xenograft models</title><author>Futami, Kazunobu ; Kumagai, Emi ; Makino, Hiroshi ; Sato, Ayumi ; Takagi, Motoki ; Shimamoto, Akira ; Furuichi, Yasuhiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c6024-4f9877d2e90bf1b9f7791682b49ccfe573702663e129e46cb7be6cc921e053683</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Biological and medical sciences</topic><topic>Carcinoma, Hepatocellular - enzymology</topic><topic>Carcinoma, Hepatocellular - genetics</topic><topic>Carcinoma, Hepatocellular - therapy</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>Colorectal Neoplasms - enzymology</topic><topic>Colorectal Neoplasms - genetics</topic><topic>Colorectal Neoplasms - therapy</topic><topic>Flow Cytometry</topic><topic>Humans</topic><topic>Immunoenzyme Techniques</topic><topic>Liposomes</topic><topic>Liver Neoplasms, Experimental - genetics</topic><topic>Liver Neoplasms, Experimental - secondary</topic><topic>Liver Neoplasms, Experimental - therapy</topic><topic>Lung Neoplasms - enzymology</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - therapy</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Neoplasms, Experimental - drug therapy</topic><topic>Neoplasms, Experimental - enzymology</topic><topic>Neoplasms, Experimental - genetics</topic><topic>Original /Report</topic><topic>Pancreatic Neoplasms - enzymology</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - therapy</topic><topic>Polyethyleneimine - chemistry</topic><topic>RecQ Helicases - antagonists & inhibitors</topic><topic>RecQ Helicases - genetics</topic><topic>RecQ Helicases - metabolism</topic><topic>Reverse Transcriptase Polymerase Chain Reaction</topic><topic>RNA, Messenger - genetics</topic><topic>RNA, Messenger - metabolism</topic><topic>RNA, Small Interfering - pharmacology</topic><topic>Tumors</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Futami, Kazunobu</creatorcontrib><creatorcontrib>Kumagai, Emi</creatorcontrib><creatorcontrib>Makino, Hiroshi</creatorcontrib><creatorcontrib>Sato, Ayumi</creatorcontrib><creatorcontrib>Takagi, Motoki</creatorcontrib><creatorcontrib>Shimamoto, Akira</creatorcontrib><creatorcontrib>Furuichi, Yasuhiro</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext_linktorsrc</fulltext></delivery><addata><au>Futami, Kazunobu</au><au>Kumagai, Emi</au><au>Makino, Hiroshi</au><au>Sato, Ayumi</au><au>Takagi, Motoki</au><au>Shimamoto, Akira</au><au>Furuichi, Yasuhiro</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anticancer activity of RecQL1 helicase siRNA in mouse xenograft models</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2008-06</date><risdate>2008</risdate><volume>99</volume><issue>6</issue><spage>1227</spage><epage>1236</epage><pages>1227-1236</pages><issn>1347-9032</issn><issn>1349-7006</issn><eissn>1349-7006</eissn><abstract>Small interfering RNAs (siRNAs) are expected to have a medical application in human therapy as drugs with a high specificity for their molecular target mRNAs. RecQL1 DNA helicase in the human RecQ helicase family participates in DNA repair and recombination pathways in the cell cycle of replication. Silencing the RecQL1 expression by RecQL1‐siRNA induces mitotic death in vitro specifically in growing cancer cells. By contrast, the same RecQL1 silencing does not affect the growth of normal cells, emphasizing that RecQL1 helicase is an ideal molecular target for cancer therapy. In this study, we show that local and systemic administration of RecQL1‐siRNA mixed with polyethyleneimine polymer or cationic liposomes prevented cancer cell proliferation in vivo in mouse models of cancer without noticeable adverse effects. The results indicate that RecQL1‐siRNA in a complex with a cationic polymer is a very promising anticancer drug candidate, and that in particular, RecQL1‐siRNA formulated with a cationic liposome has an enormous potential to be used by intravenous injection for therapy specific for liver cancers, including metastasized cancers from the colon and pancreas. (Cancer Sci 2008; 99: 1227–1236)</abstract><cop>Melbourne, Australia</cop><pub>Blackwell Publishing Asia</pub><pmid>18422747</pmid><doi>10.1111/j.1349-7006.2008.00794.x</doi><tpages>10</tpages></addata></record> |
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| identifier | ISSN: 1347-9032 |
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| issn | 1347-9032 1349-7006 1349-7006 |
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| source | Open Access: Wiley-Blackwell Open Access Journals |
| subjects | Animals Biological and medical sciences Carcinoma, Hepatocellular - enzymology Carcinoma, Hepatocellular - genetics Carcinoma, Hepatocellular - therapy Cell Line, Tumor Cell Proliferation Colorectal Neoplasms - enzymology Colorectal Neoplasms - genetics Colorectal Neoplasms - therapy Flow Cytometry Humans Immunoenzyme Techniques Liposomes Liver Neoplasms, Experimental - genetics Liver Neoplasms, Experimental - secondary Liver Neoplasms, Experimental - therapy Lung Neoplasms - enzymology Lung Neoplasms - genetics Lung Neoplasms - therapy Male Medical sciences Mice Mice, Inbred BALB C Mice, Nude Neoplasms, Experimental - drug therapy Neoplasms, Experimental - enzymology Neoplasms, Experimental - genetics Original /Report Pancreatic Neoplasms - enzymology Pancreatic Neoplasms - genetics Pancreatic Neoplasms - therapy Polyethyleneimine - chemistry RecQ Helicases - antagonists & inhibitors RecQ Helicases - genetics RecQ Helicases - metabolism Reverse Transcriptase Polymerase Chain Reaction RNA, Messenger - genetics RNA, Messenger - metabolism RNA, Small Interfering - pharmacology Tumors Xenograft Model Antitumor Assays |
| title | Anticancer activity of RecQL1 helicase siRNA in mouse xenograft models |
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