Ambivalent effects of atorvastatin on angiogenesis, epidermal cell proliferation and tumorgenesis in animal models
A growing body of preclinical data indicates that statins may possess antineoplastic properties; however, some studies have raised the possibility that statins may also have carcinogenic potential. An air pouch model was used for angiogenesis. Single or multiple applications of croton oil on the bac...
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| Veröffentlicht in: | Iranian biomedical journal 2012, Vol.16 (2), p.59-67 |
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| creator | Garjani, Alireza Rezazadeh, Hassan Andalib, Sina Ziaee, Mojtaba Doustar, Yousef Soraya, Hamid Garjani, Mehraveh Khorrami, Arash Asadpoor, Mostafa Maleki-Dizaji, Nasrin |
| description | A growing body of preclinical data indicates that statins may possess antineoplastic properties; however, some studies have raised the possibility that statins may also have carcinogenic potential.
An air pouch model was used for angiogenesis. Single or multiple applications of croton oil on the back of Swiss albino mice with or without initiation by dimethylbenz(a)antheracene (DMBA) were used to evaluate the skin tumorgenesis, ultrastructural and histological alterations.
Atorvastatin (orally, 10 mg/kg/day) produced a significant (P |
| doi_str_mv | 10.6091/IBJ.1017.2012 |
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An air pouch model was used for angiogenesis. Single or multiple applications of croton oil on the back of Swiss albino mice with or without initiation by dimethylbenz(a)antheracene (DMBA) were used to evaluate the skin tumorgenesis, ultrastructural and histological alterations.
Atorvastatin (orally, 10 mg/kg/day) produced a significant (P<0.05) reduction in angiogenesis. Concurrent administration of mevalonate reversed the anti-angiogenic effect of atorvastatin. However, local injection of atorvastatin (200 μg) into the pouches induced a significant (P<0.5) increase in angiogenesis that was not reversed by co-administration of mevalonate. The disturbance of cell polarity, inflammatory response, thickness of epidermal layer, and mitotic index induced by croton oil were inhibited markedly and dose-dependently (P<0.001) by pre-treatment with atorvastatin. In spite of the strong anti-inflammatory and anti-proliferative effects of atorvastatin on epidermal cell proliferation, it was identified that the same doses of atorvastatin in DMBA-initiated and croton oil-promoted skin tumorgenesis in mice increased the incidence of tumors and their conversion into malignant carcinoma.
The reasons for these discrepancies remain unclear, and could be related to ambivalent effects of atorvastatin on angiogenesis or to specific differences in the experimental conditions. It is suggested that the pro-angiogenic effect of the drug, which could be responsible for promotion of skin tumors, is independent of the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibition that can be mediated directly by atorvastatin.</description><identifier>ISSN: 1028-852X</identifier><identifier>EISSN: 2008-823X</identifier><identifier>DOI: 10.6091/IBJ.1017.2012</identifier><identifier>PMID: 22801278</identifier><language>eng</language><publisher>Iran: Pasteur Institute of Iran</publisher><subject>9,10-Dimethyl-1,2-benzanthracene ; Animals ; Atorvastatin Calcium ; Cell Proliferation - drug effects ; Croton Oil ; Epidermis - cytology ; Epidermis - drug effects ; Female ; Heptanoic Acids - administration & dosage ; Heptanoic Acids - pharmacology ; Hydroxymethylglutaryl CoA Reductases - metabolism ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage ; Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology ; Male ; Mevalonic Acid - pharmacology ; Mice ; Neovascularization, Pathologic ; Original ; Pyrroles - administration & dosage ; Pyrroles - pharmacology ; Rats ; Rats, Wistar ; Skin Neoplasms - blood supply ; Skin Neoplasms - chemically induced ; Skin Neoplasms - pathology</subject><ispartof>Iranian biomedical journal, 2012, Vol.16 (2), p.59-67</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c258t-8f0d104eae032f864befb92e055af21155e1c8aaaea152fff1d78209f7a41cbe3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3600953/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3600953/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,860,881,4010,27900,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22801278$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Garjani, Alireza</creatorcontrib><creatorcontrib>Rezazadeh, Hassan</creatorcontrib><creatorcontrib>Andalib, Sina</creatorcontrib><creatorcontrib>Ziaee, Mojtaba</creatorcontrib><creatorcontrib>Doustar, Yousef</creatorcontrib><creatorcontrib>Soraya, Hamid</creatorcontrib><creatorcontrib>Garjani, Mehraveh</creatorcontrib><creatorcontrib>Khorrami, Arash</creatorcontrib><creatorcontrib>Asadpoor, Mostafa</creatorcontrib><creatorcontrib>Maleki-Dizaji, Nasrin</creatorcontrib><title>Ambivalent effects of atorvastatin on angiogenesis, epidermal cell proliferation and tumorgenesis in animal models</title><title>Iranian biomedical journal</title><addtitle>Iran Biomed J</addtitle><description>A growing body of preclinical data indicates that statins may possess antineoplastic properties; however, some studies have raised the possibility that statins may also have carcinogenic potential.
An air pouch model was used for angiogenesis. Single or multiple applications of croton oil on the back of Swiss albino mice with or without initiation by dimethylbenz(a)antheracene (DMBA) were used to evaluate the skin tumorgenesis, ultrastructural and histological alterations.
Atorvastatin (orally, 10 mg/kg/day) produced a significant (P<0.05) reduction in angiogenesis. Concurrent administration of mevalonate reversed the anti-angiogenic effect of atorvastatin. However, local injection of atorvastatin (200 μg) into the pouches induced a significant (P<0.5) increase in angiogenesis that was not reversed by co-administration of mevalonate. The disturbance of cell polarity, inflammatory response, thickness of epidermal layer, and mitotic index induced by croton oil were inhibited markedly and dose-dependently (P<0.001) by pre-treatment with atorvastatin. In spite of the strong anti-inflammatory and anti-proliferative effects of atorvastatin on epidermal cell proliferation, it was identified that the same doses of atorvastatin in DMBA-initiated and croton oil-promoted skin tumorgenesis in mice increased the incidence of tumors and their conversion into malignant carcinoma.
The reasons for these discrepancies remain unclear, and could be related to ambivalent effects of atorvastatin on angiogenesis or to specific differences in the experimental conditions. It is suggested that the pro-angiogenic effect of the drug, which could be responsible for promotion of skin tumors, is independent of the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibition that can be mediated directly by atorvastatin.</description><subject>9,10-Dimethyl-1,2-benzanthracene</subject><subject>Animals</subject><subject>Atorvastatin Calcium</subject><subject>Cell Proliferation - drug effects</subject><subject>Croton Oil</subject><subject>Epidermis - cytology</subject><subject>Epidermis - drug effects</subject><subject>Female</subject><subject>Heptanoic Acids - administration & dosage</subject><subject>Heptanoic Acids - pharmacology</subject><subject>Hydroxymethylglutaryl CoA Reductases - metabolism</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage</subject><subject>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</subject><subject>Male</subject><subject>Mevalonic Acid - pharmacology</subject><subject>Mice</subject><subject>Neovascularization, Pathologic</subject><subject>Original</subject><subject>Pyrroles - administration & dosage</subject><subject>Pyrroles - pharmacology</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Skin Neoplasms - blood supply</subject><subject>Skin Neoplasms - chemically induced</subject><subject>Skin Neoplasms - pathology</subject><issn>1028-852X</issn><issn>2008-823X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkE1PwzAMQCMEYmNw5IryA-hw0mVNL0hj4mNoEheQdqvc1hlBaTMlZRL_ng4GgpMt-_nJNmPnAsZTyMXV4uZxLEBkYwlCHrChBNCJlunqkA0FyD5XcjVgJzG-AaRKZNkxG0ipezrTQxZmTWm36KjtOBlDVRe5Nxw7H7YYO-xsy33LsV1bv6aWoo2XnDa2ptCg4xU5xzfBO2so9PAXWvPuvfFhj3O7q9kd3fiaXDxlRwZdpLN9HLGXu9vn-UOyfLpfzGfLpJJKd4k2UAuYEBKk0ujppCRT5pJAKTRSCKVIVBoRCYWSxhhRZ1pCbjKciKqkdMSuv72b97KhuupPDOiKTeh3CR-FR1v877T2tVj7bZFOAXKV9oKLv4LfyZ_vpZ-V13Zg</recordid><startdate>2012</startdate><enddate>2012</enddate><creator>Garjani, Alireza</creator><creator>Rezazadeh, Hassan</creator><creator>Andalib, Sina</creator><creator>Ziaee, Mojtaba</creator><creator>Doustar, Yousef</creator><creator>Soraya, Hamid</creator><creator>Garjani, Mehraveh</creator><creator>Khorrami, Arash</creator><creator>Asadpoor, Mostafa</creator><creator>Maleki-Dizaji, Nasrin</creator><general>Pasteur Institute of Iran</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>5PM</scope></search><sort><creationdate>2012</creationdate><title>Ambivalent effects of atorvastatin on angiogenesis, epidermal cell proliferation and tumorgenesis in animal models</title><author>Garjani, Alireza ; Rezazadeh, Hassan ; Andalib, Sina ; Ziaee, Mojtaba ; Doustar, Yousef ; Soraya, Hamid ; Garjani, Mehraveh ; Khorrami, Arash ; Asadpoor, Mostafa ; Maleki-Dizaji, Nasrin</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c258t-8f0d104eae032f864befb92e055af21155e1c8aaaea152fff1d78209f7a41cbe3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>9,10-Dimethyl-1,2-benzanthracene</topic><topic>Animals</topic><topic>Atorvastatin Calcium</topic><topic>Cell Proliferation - drug effects</topic><topic>Croton Oil</topic><topic>Epidermis - cytology</topic><topic>Epidermis - drug effects</topic><topic>Female</topic><topic>Heptanoic Acids - administration & dosage</topic><topic>Heptanoic Acids - pharmacology</topic><topic>Hydroxymethylglutaryl CoA Reductases - metabolism</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage</topic><topic>Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology</topic><topic>Male</topic><topic>Mevalonic Acid - pharmacology</topic><topic>Mice</topic><topic>Neovascularization, Pathologic</topic><topic>Original</topic><topic>Pyrroles - administration & dosage</topic><topic>Pyrroles - pharmacology</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Skin Neoplasms - blood supply</topic><topic>Skin Neoplasms - chemically induced</topic><topic>Skin Neoplasms - pathology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Garjani, Alireza</creatorcontrib><creatorcontrib>Rezazadeh, Hassan</creatorcontrib><creatorcontrib>Andalib, Sina</creatorcontrib><creatorcontrib>Ziaee, Mojtaba</creatorcontrib><creatorcontrib>Doustar, Yousef</creatorcontrib><creatorcontrib>Soraya, Hamid</creatorcontrib><creatorcontrib>Garjani, Mehraveh</creatorcontrib><creatorcontrib>Khorrami, Arash</creatorcontrib><creatorcontrib>Asadpoor, Mostafa</creatorcontrib><creatorcontrib>Maleki-Dizaji, Nasrin</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Iranian biomedical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Garjani, Alireza</au><au>Rezazadeh, Hassan</au><au>Andalib, Sina</au><au>Ziaee, Mojtaba</au><au>Doustar, Yousef</au><au>Soraya, Hamid</au><au>Garjani, Mehraveh</au><au>Khorrami, Arash</au><au>Asadpoor, Mostafa</au><au>Maleki-Dizaji, Nasrin</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Ambivalent effects of atorvastatin on angiogenesis, epidermal cell proliferation and tumorgenesis in animal models</atitle><jtitle>Iranian biomedical journal</jtitle><addtitle>Iran Biomed J</addtitle><date>2012</date><risdate>2012</risdate><volume>16</volume><issue>2</issue><spage>59</spage><epage>67</epage><pages>59-67</pages><issn>1028-852X</issn><eissn>2008-823X</eissn><abstract>A growing body of preclinical data indicates that statins may possess antineoplastic properties; however, some studies have raised the possibility that statins may also have carcinogenic potential.
An air pouch model was used for angiogenesis. Single or multiple applications of croton oil on the back of Swiss albino mice with or without initiation by dimethylbenz(a)antheracene (DMBA) were used to evaluate the skin tumorgenesis, ultrastructural and histological alterations.
Atorvastatin (orally, 10 mg/kg/day) produced a significant (P<0.05) reduction in angiogenesis. Concurrent administration of mevalonate reversed the anti-angiogenic effect of atorvastatin. However, local injection of atorvastatin (200 μg) into the pouches induced a significant (P<0.5) increase in angiogenesis that was not reversed by co-administration of mevalonate. The disturbance of cell polarity, inflammatory response, thickness of epidermal layer, and mitotic index induced by croton oil were inhibited markedly and dose-dependently (P<0.001) by pre-treatment with atorvastatin. In spite of the strong anti-inflammatory and anti-proliferative effects of atorvastatin on epidermal cell proliferation, it was identified that the same doses of atorvastatin in DMBA-initiated and croton oil-promoted skin tumorgenesis in mice increased the incidence of tumors and their conversion into malignant carcinoma.
The reasons for these discrepancies remain unclear, and could be related to ambivalent effects of atorvastatin on angiogenesis or to specific differences in the experimental conditions. It is suggested that the pro-angiogenic effect of the drug, which could be responsible for promotion of skin tumors, is independent of the 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase inhibition that can be mediated directly by atorvastatin.</abstract><cop>Iran</cop><pub>Pasteur Institute of Iran</pub><pmid>22801278</pmid><doi>10.6091/IBJ.1017.2012</doi><tpages>9</tpages></addata></record> |
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| ispartof | Iranian biomedical journal, 2012, Vol.16 (2), p.59-67 |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | 9,10-Dimethyl-1,2-benzanthracene Animals Atorvastatin Calcium Cell Proliferation - drug effects Croton Oil Epidermis - cytology Epidermis - drug effects Female Heptanoic Acids - administration & dosage Heptanoic Acids - pharmacology Hydroxymethylglutaryl CoA Reductases - metabolism Hydroxymethylglutaryl-CoA Reductase Inhibitors - administration & dosage Hydroxymethylglutaryl-CoA Reductase Inhibitors - pharmacology Male Mevalonic Acid - pharmacology Mice Neovascularization, Pathologic Original Pyrroles - administration & dosage Pyrroles - pharmacology Rats Rats, Wistar Skin Neoplasms - blood supply Skin Neoplasms - chemically induced Skin Neoplasms - pathology |
| title | Ambivalent effects of atorvastatin on angiogenesis, epidermal cell proliferation and tumorgenesis in animal models |
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