Cerivastatin Triggers Tumor-specific Apoptosis with Higher Efficacy than Lovastatin
The statin family of drugs inhibits 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, the rate-limiting enzyme of the mevalonate pathway, and is used clinically as a safe and effective approach in the control of hypercholesterolemia. We have shown previously (Dimitroulakos, J., Nohynek, D., Backwa...
Gespeichert in:
Veröffentlicht in: | Clinical cancer research 2001-07, Vol.7 (7), p.2067-2075 |
---|---|
Hauptverfasser: | , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 2075 |
---|---|
container_issue | 7 |
container_start_page | 2067 |
container_title | Clinical cancer research |
container_volume | 7 |
creator | Wong, W W Tan, M M Xia, Z Dimitroulakos, J Minden, M D Penn, L Z |
description | The statin family of drugs inhibits 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, the rate-limiting enzyme of the mevalonate
pathway, and is used clinically as a safe and effective approach in the control of hypercholesterolemia. We have shown previously
(Dimitroulakos, J., Nohynek, D., Backway, K. L., Hedley, D. W., Yeger, H., Freedman, M. H., Minden, M D., and Penn, L. Z.
Increased sensitivity of acute myelogenous leukemias to lovastatin-induced apoptosis: a potential therapeutic approach. Blood,
93: 1308–1318, 1999) that lovastatin, a prototypic member of the statin family, can induce apoptosis of human acute myeloid leukemia
(AML) cells in a sensitive and specific manner. In the present study, we evaluated the relative potency and mechanism of action
of the newer synthetic statins, fluvastatin, atorvastatin, and cerivastatin, to trigger tumor-specific apoptosis. Cerivastatin
is at least 10 times more potent than the other statins at inducing apoptosis in AML cell lines. Cerivastatin-induced apoptosis
is reversible with the addition of the immediate product of the HMG-CoA reductase reaction, mevalonate, or with a distal product
of the pathway, geranylgeranyl pyrophosphate. This suggests protein geranylgeranylation is an essential downstream component
of the mevalonate pathway for cerivastatin similar to lovastatin-induced apoptosis. The enhanced potency of cerivastatin expands
the number of AML patient samples as well as the types of malignancies, which respond to statin-induced apoptosis with acute
sensitivity. Cells derived from acute lymphocytic leukemia are only weakly sensitive to lovastatin cytotoxicity but show robust
response to cerivastatin. Importantly, cerivastatin is not cytotoxic to nontransformed human bone marrow progenitors. These
results strongly support the further testing of cerivastatin as a novel anticancer therapeutic alone and in combination with
other agents in vivo . |
format | Article |
fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_proquest_miscellaneous_70992120</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>70992120</sourcerecordid><originalsourceid>FETCH-LOGICAL-h268t-e377d84d39154433c97d2a42e1566732fd76a7467c46b2e21f775e766278c5673</originalsourceid><addsrcrecordid>eNpF0E1Lw0AQBuAgiq3VvyB7ED0F9nuSYynVCgUP1nPYbibNStLE3cTSf-9CW2QOMzAPw_BeJVOmFKSCa3UdZwpZSqXgk-QuhG9KmWRU3iYTxqTMcq6myecCvfs1YTCD25ONd7sd-kA2Y9v5NPRoXeUsmfddP3TBBXJwQ01WblejJ8sq7ow9kqE2e7LuLmfuk5vKNAEfzn2WfL0uN4tVuv54e1_M12nNdTakKADKTJYiZ0pKIWwOJTeSI1Nag-BVCdqA1GCl3nLkrAJQCFpzyKyKYpY8n-72vvsZMQxF64LFpjF77MZQAM1zzjiN8PEMx22LZdF71xp_LC4xRPB0BiZY01Te7K0L_45mguc8spcTq2MAB-exsBGi9xjQeFsXEIvT-NoffIhzug</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>70992120</pqid></control><display><type>article</type><title>Cerivastatin Triggers Tumor-specific Apoptosis with Higher Efficacy than Lovastatin</title><source>MEDLINE</source><source>American Association for Cancer Research</source><source>EZB-FREE-00999 freely available EZB journals</source><source>Alma/SFX Local Collection</source><creator>Wong, W W ; Tan, M M ; Xia, Z ; Dimitroulakos, J ; Minden, M D ; Penn, L Z</creator><creatorcontrib>Wong, W W ; Tan, M M ; Xia, Z ; Dimitroulakos, J ; Minden, M D ; Penn, L Z</creatorcontrib><description>The statin family of drugs inhibits 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, the rate-limiting enzyme of the mevalonate
pathway, and is used clinically as a safe and effective approach in the control of hypercholesterolemia. We have shown previously
(Dimitroulakos, J., Nohynek, D., Backway, K. L., Hedley, D. W., Yeger, H., Freedman, M. H., Minden, M D., and Penn, L. Z.
Increased sensitivity of acute myelogenous leukemias to lovastatin-induced apoptosis: a potential therapeutic approach. Blood,
93: 1308–1318, 1999) that lovastatin, a prototypic member of the statin family, can induce apoptosis of human acute myeloid leukemia
(AML) cells in a sensitive and specific manner. In the present study, we evaluated the relative potency and mechanism of action
of the newer synthetic statins, fluvastatin, atorvastatin, and cerivastatin, to trigger tumor-specific apoptosis. Cerivastatin
is at least 10 times more potent than the other statins at inducing apoptosis in AML cell lines. Cerivastatin-induced apoptosis
is reversible with the addition of the immediate product of the HMG-CoA reductase reaction, mevalonate, or with a distal product
of the pathway, geranylgeranyl pyrophosphate. This suggests protein geranylgeranylation is an essential downstream component
of the mevalonate pathway for cerivastatin similar to lovastatin-induced apoptosis. The enhanced potency of cerivastatin expands
the number of AML patient samples as well as the types of malignancies, which respond to statin-induced apoptosis with acute
sensitivity. Cells derived from acute lymphocytic leukemia are only weakly sensitive to lovastatin cytotoxicity but show robust
response to cerivastatin. Importantly, cerivastatin is not cytotoxic to nontransformed human bone marrow progenitors. These
results strongly support the further testing of cerivastatin as a novel anticancer therapeutic alone and in combination with
other agents in vivo .</description><identifier>ISSN: 1078-0432</identifier><identifier>EISSN: 1557-3265</identifier><identifier>PMID: 11448925</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>Acute Disease ; Antineoplastic agents ; Apoptosis - drug effects ; Atorvastatin Calcium ; Biological and medical sciences ; Cell Division - drug effects ; Chemotherapy ; Dose-Response Relationship, Drug ; Fatty Acids, Monounsaturated - pharmacology ; Heptanoic Acids - pharmacology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology ; Indoles - pharmacology ; Leukemia, Myeloid - drug therapy ; Leukemia, Myeloid - pathology ; Lovastatin - pharmacology ; Medical sciences ; Neoplasms - drug therapy ; Neoplasms - pathology ; Pharmacology. Drug treatments ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy ; Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology ; Pyridines - pharmacology ; Pyrroles - pharmacology ; Sensitivity and Specificity ; Tumor Cells, Cultured</subject><ispartof>Clinical cancer research, 2001-07, Vol.7 (7), p.2067-2075</ispartof><rights>2001 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1083292$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11448925$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wong, W W</creatorcontrib><creatorcontrib>Tan, M M</creatorcontrib><creatorcontrib>Xia, Z</creatorcontrib><creatorcontrib>Dimitroulakos, J</creatorcontrib><creatorcontrib>Minden, M D</creatorcontrib><creatorcontrib>Penn, L Z</creatorcontrib><title>Cerivastatin Triggers Tumor-specific Apoptosis with Higher Efficacy than Lovastatin</title><title>Clinical cancer research</title><addtitle>Clin Cancer Res</addtitle><description>The statin family of drugs inhibits 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, the rate-limiting enzyme of the mevalonate
pathway, and is used clinically as a safe and effective approach in the control of hypercholesterolemia. We have shown previously
(Dimitroulakos, J., Nohynek, D., Backway, K. L., Hedley, D. W., Yeger, H., Freedman, M. H., Minden, M D., and Penn, L. Z.
Increased sensitivity of acute myelogenous leukemias to lovastatin-induced apoptosis: a potential therapeutic approach. Blood,
93: 1308–1318, 1999) that lovastatin, a prototypic member of the statin family, can induce apoptosis of human acute myeloid leukemia
(AML) cells in a sensitive and specific manner. In the present study, we evaluated the relative potency and mechanism of action
of the newer synthetic statins, fluvastatin, atorvastatin, and cerivastatin, to trigger tumor-specific apoptosis. Cerivastatin
is at least 10 times more potent than the other statins at inducing apoptosis in AML cell lines. Cerivastatin-induced apoptosis
is reversible with the addition of the immediate product of the HMG-CoA reductase reaction, mevalonate, or with a distal product
of the pathway, geranylgeranyl pyrophosphate. This suggests protein geranylgeranylation is an essential downstream component
of the mevalonate pathway for cerivastatin similar to lovastatin-induced apoptosis. The enhanced potency of cerivastatin expands
the number of AML patient samples as well as the types of malignancies, which respond to statin-induced apoptosis with acute
sensitivity. Cells derived from acute lymphocytic leukemia are only weakly sensitive to lovastatin cytotoxicity but show robust
response to cerivastatin. Importantly, cerivastatin is not cytotoxic to nontransformed human bone marrow progenitors. These
results strongly support the further testing of cerivastatin as a novel anticancer therapeutic alone and in combination with
other agents in vivo .</description><subject>Acute Disease</subject><subject>Antineoplastic agents</subject><subject>Apoptosis - drug effects</subject><subject>Atorvastatin Calcium</subject><subject>Biological and medical sciences</subject><subject>Cell Division - drug effects</subject><subject>Chemotherapy</subject><subject>Dose-Response Relationship, Drug</subject><subject>Fatty Acids, Monounsaturated - pharmacology</subject><subject>Heptanoic Acids - pharmacology</subject><subject>Humans</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</subject><subject>Indoles - pharmacology</subject><subject>Leukemia, Myeloid - drug therapy</subject><subject>Leukemia, Myeloid - pathology</subject><subject>Lovastatin - pharmacology</subject><subject>Medical sciences</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - pathology</subject><subject>Pharmacology. Drug treatments</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</subject><subject>Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology</subject><subject>Pyridines - pharmacology</subject><subject>Pyrroles - pharmacology</subject><subject>Sensitivity and Specificity</subject><subject>Tumor Cells, Cultured</subject><issn>1078-0432</issn><issn>1557-3265</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2001</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpF0E1Lw0AQBuAgiq3VvyB7ED0F9nuSYynVCgUP1nPYbibNStLE3cTSf-9CW2QOMzAPw_BeJVOmFKSCa3UdZwpZSqXgk-QuhG9KmWRU3iYTxqTMcq6myecCvfs1YTCD25ONd7sd-kA2Y9v5NPRoXeUsmfddP3TBBXJwQ01WblejJ8sq7ow9kqE2e7LuLmfuk5vKNAEfzn2WfL0uN4tVuv54e1_M12nNdTakKADKTJYiZ0pKIWwOJTeSI1Nag-BVCdqA1GCl3nLkrAJQCFpzyKyKYpY8n-72vvsZMQxF64LFpjF77MZQAM1zzjiN8PEMx22LZdF71xp_LC4xRPB0BiZY01Te7K0L_45mguc8spcTq2MAB-exsBGi9xjQeFsXEIvT-NoffIhzug</recordid><startdate>20010701</startdate><enddate>20010701</enddate><creator>Wong, W W</creator><creator>Tan, M M</creator><creator>Xia, Z</creator><creator>Dimitroulakos, J</creator><creator>Minden, M D</creator><creator>Penn, L Z</creator><general>American Association for Cancer Research</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20010701</creationdate><title>Cerivastatin Triggers Tumor-specific Apoptosis with Higher Efficacy than Lovastatin</title><author>Wong, W W ; Tan, M M ; Xia, Z ; Dimitroulakos, J ; Minden, M D ; Penn, L Z</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h268t-e377d84d39154433c97d2a42e1566732fd76a7467c46b2e21f775e766278c5673</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2001</creationdate><topic>Acute Disease</topic><topic>Antineoplastic agents</topic><topic>Apoptosis - drug effects</topic><topic>Atorvastatin Calcium</topic><topic>Biological and medical sciences</topic><topic>Cell Division - drug effects</topic><topic>Chemotherapy</topic><topic>Dose-Response Relationship, Drug</topic><topic>Fatty Acids, Monounsaturated - pharmacology</topic><topic>Heptanoic Acids - pharmacology</topic><topic>Humans</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</topic><topic>Indoles - pharmacology</topic><topic>Leukemia, Myeloid - drug therapy</topic><topic>Leukemia, Myeloid - pathology</topic><topic>Lovastatin - pharmacology</topic><topic>Medical sciences</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - pathology</topic><topic>Pharmacology. Drug treatments</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy</topic><topic>Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology</topic><topic>Pyridines - pharmacology</topic><topic>Pyrroles - pharmacology</topic><topic>Sensitivity and Specificity</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wong, W W</creatorcontrib><creatorcontrib>Tan, M M</creatorcontrib><creatorcontrib>Xia, Z</creatorcontrib><creatorcontrib>Dimitroulakos, J</creatorcontrib><creatorcontrib>Minden, M D</creatorcontrib><creatorcontrib>Penn, L Z</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>MEDLINE - Academic</collection><jtitle>Clinical cancer research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wong, W W</au><au>Tan, M M</au><au>Xia, Z</au><au>Dimitroulakos, J</au><au>Minden, M D</au><au>Penn, L Z</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Cerivastatin Triggers Tumor-specific Apoptosis with Higher Efficacy than Lovastatin</atitle><jtitle>Clinical cancer research</jtitle><addtitle>Clin Cancer Res</addtitle><date>2001-07-01</date><risdate>2001</risdate><volume>7</volume><issue>7</issue><spage>2067</spage><epage>2075</epage><pages>2067-2075</pages><issn>1078-0432</issn><eissn>1557-3265</eissn><abstract>The statin family of drugs inhibits 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase, the rate-limiting enzyme of the mevalonate
pathway, and is used clinically as a safe and effective approach in the control of hypercholesterolemia. We have shown previously
(Dimitroulakos, J., Nohynek, D., Backway, K. L., Hedley, D. W., Yeger, H., Freedman, M. H., Minden, M D., and Penn, L. Z.
Increased sensitivity of acute myelogenous leukemias to lovastatin-induced apoptosis: a potential therapeutic approach. Blood,
93: 1308–1318, 1999) that lovastatin, a prototypic member of the statin family, can induce apoptosis of human acute myeloid leukemia
(AML) cells in a sensitive and specific manner. In the present study, we evaluated the relative potency and mechanism of action
of the newer synthetic statins, fluvastatin, atorvastatin, and cerivastatin, to trigger tumor-specific apoptosis. Cerivastatin
is at least 10 times more potent than the other statins at inducing apoptosis in AML cell lines. Cerivastatin-induced apoptosis
is reversible with the addition of the immediate product of the HMG-CoA reductase reaction, mevalonate, or with a distal product
of the pathway, geranylgeranyl pyrophosphate. This suggests protein geranylgeranylation is an essential downstream component
of the mevalonate pathway for cerivastatin similar to lovastatin-induced apoptosis. The enhanced potency of cerivastatin expands
the number of AML patient samples as well as the types of malignancies, which respond to statin-induced apoptosis with acute
sensitivity. Cells derived from acute lymphocytic leukemia are only weakly sensitive to lovastatin cytotoxicity but show robust
response to cerivastatin. Importantly, cerivastatin is not cytotoxic to nontransformed human bone marrow progenitors. These
results strongly support the further testing of cerivastatin as a novel anticancer therapeutic alone and in combination with
other agents in vivo .</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>11448925</pmid><tpages>9</tpages></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1078-0432 |
ispartof | Clinical cancer research, 2001-07, Vol.7 (7), p.2067-2075 |
issn | 1078-0432 1557-3265 |
language | eng |
recordid | cdi_proquest_miscellaneous_70992120 |
source | MEDLINE; American Association for Cancer Research; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
subjects | Acute Disease Antineoplastic agents Apoptosis - drug effects Atorvastatin Calcium Biological and medical sciences Cell Division - drug effects Chemotherapy Dose-Response Relationship, Drug Fatty Acids, Monounsaturated - pharmacology Heptanoic Acids - pharmacology Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology Indoles - pharmacology Leukemia, Myeloid - drug therapy Leukemia, Myeloid - pathology Lovastatin - pharmacology Medical sciences Neoplasms - drug therapy Neoplasms - pathology Pharmacology. Drug treatments Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy Precursor Cell Lymphoblastic Leukemia-Lymphoma - pathology Pyridines - pharmacology Pyrroles - pharmacology Sensitivity and Specificity Tumor Cells, Cultured |
title | Cerivastatin Triggers Tumor-specific Apoptosis with Higher Efficacy than Lovastatin |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-25T00%3A07%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Cerivastatin%20Triggers%20Tumor-specific%20Apoptosis%20with%20Higher%20Efficacy%20than%20Lovastatin&rft.jtitle=Clinical%20cancer%20research&rft.au=Wong,%20W%20W&rft.date=2001-07-01&rft.volume=7&rft.issue=7&rft.spage=2067&rft.epage=2075&rft.pages=2067-2075&rft.issn=1078-0432&rft.eissn=1557-3265&rft_id=info:doi/&rft_dat=%3Cproquest_pubme%3E70992120%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=70992120&rft_id=info:pmid/11448925&rfr_iscdi=true |