Inhibition of skin tumorigenesis by Rosemary and its constituents carnosol and ursolic acid
A methanol extract of the leaves of the plant Rosmarinus officinalis L. (rosemary) was evaluated for its effects on tumor initiation and promotion in mouse skin. Application of rosemary to mouse skin inhibited the covalent binding of benzo(a)pyrene [B(a)P] to epidermal DNA and inhibited tumor initia...
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| Veröffentlicht in: | Cancer research (Chicago, Ill.) Ill.), 1994-02, Vol.54 (3), p.701-708 |
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| creator | MOU-TUAN HUANG CHI-TANG HO ZHI YUAN WANG FERRARO, T YOU-RONG LOU STAUBER, K WEI MA GEORGIADIS, C LASKIN, J. D CONNEY, A. H |
| description | A methanol extract of the leaves of the plant Rosmarinus officinalis L. (rosemary) was evaluated for its effects on tumor initiation and promotion in mouse skin. Application of rosemary to mouse skin inhibited the covalent binding of benzo(a)pyrene [B(a)P] to epidermal DNA and inhibited tumor initiation by B(a)P and 7,12-dimethylbenz[a]anthracene (DMBA). Topical application of 20 nmol B(a)P to the backs of mice once weekly for 10 weeks, followed 1 week later by promotion with 15 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) twice weekly for 21 weeks, resulted in the formation of 7.1 tumors per mouse. In a parallel group of animals that were treated topically with 1.2 or 3.6 mg of rosemary 5 min prior to each application of B(a)P, the number of tumors per mouse was decreased by 54 or 64%, respectively. Application of rosemary to mouse skin also inhibited TPA-induced ornithine decarboxylase activity, TPA-induced inflammation, arachidonic acid-induced inflammation, TPA-induced hyperplasia, and TPA-induced tumor promotion. Mice initiated with 200 nmol DMBA and promoted with 5 nmol TPA twice weekly for 19 weeks developed an average of 17.2 skin tumors per mouse. Treatment of the DMBA-initiated mice with 0.4, 1.2, or 3.6 mg of rosemary together with 5 nmol TPA twice weekly for 19 weeks inhibited the number of TPA-induced skin tumors per mouse by 40, 68, or 99%, respectively. Topical application of carnosol or ursolic acid isolated from rosemary inhibited TPA-induced ear inflammation, ornithine decarboxylase activity, and tumor promotion. Topical application of 1, 3, or 10 mumol carnosol together with 5 nmol TPA twice weekly for 20 weeks to the backs of mice previously initiated with DMBA inhibited the number of skin tumors per mouse by 38, 63, or 78%, respectively. Topical application of 0.1, 0.3, 1, or 2 mumol ursolic acid together with 5 nmol TPA twice weekly for 20 weeks to DMBA-initiated mice inhibited the number of tumors per mouse by 45-61%. |
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D ; CONNEY, A. H</creator><creatorcontrib>MOU-TUAN HUANG ; CHI-TANG HO ; ZHI YUAN WANG ; FERRARO, T ; YOU-RONG LOU ; STAUBER, K ; WEI MA ; GEORGIADIS, C ; LASKIN, J. D ; CONNEY, A. H</creatorcontrib><description>A methanol extract of the leaves of the plant Rosmarinus officinalis L. (rosemary) was evaluated for its effects on tumor initiation and promotion in mouse skin. Application of rosemary to mouse skin inhibited the covalent binding of benzo(a)pyrene [B(a)P] to epidermal DNA and inhibited tumor initiation by B(a)P and 7,12-dimethylbenz[a]anthracene (DMBA). Topical application of 20 nmol B(a)P to the backs of mice once weekly for 10 weeks, followed 1 week later by promotion with 15 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) twice weekly for 21 weeks, resulted in the formation of 7.1 tumors per mouse. In a parallel group of animals that were treated topically with 1.2 or 3.6 mg of rosemary 5 min prior to each application of B(a)P, the number of tumors per mouse was decreased by 54 or 64%, respectively. Application of rosemary to mouse skin also inhibited TPA-induced ornithine decarboxylase activity, TPA-induced inflammation, arachidonic acid-induced inflammation, TPA-induced hyperplasia, and TPA-induced tumor promotion. Mice initiated with 200 nmol DMBA and promoted with 5 nmol TPA twice weekly for 19 weeks developed an average of 17.2 skin tumors per mouse. Treatment of the DMBA-initiated mice with 0.4, 1.2, or 3.6 mg of rosemary together with 5 nmol TPA twice weekly for 19 weeks inhibited the number of TPA-induced skin tumors per mouse by 40, 68, or 99%, respectively. Topical application of carnosol or ursolic acid isolated from rosemary inhibited TPA-induced ear inflammation, ornithine decarboxylase activity, and tumor promotion. Topical application of 1, 3, or 10 mumol carnosol together with 5 nmol TPA twice weekly for 20 weeks to the backs of mice previously initiated with DMBA inhibited the number of skin tumors per mouse by 38, 63, or 78%, respectively. Topical application of 0.1, 0.3, 1, or 2 mumol ursolic acid together with 5 nmol TPA twice weekly for 20 weeks to DMBA-initiated mice inhibited the number of tumors per mouse by 45-61%.</description><identifier>ISSN: 0008-5472</identifier><identifier>EISSN: 1538-7445</identifier><identifier>PMID: 8306331</identifier><identifier>CODEN: CNREA8</identifier><language>eng</language><publisher>Philadelphia, PA: American Association for Cancer Research</publisher><subject>9,10-Dimethyl-1,2-benzanthracene - antagonists & inhibitors ; Abietanes ; Animals ; Anticarcinogenic Agents - therapeutic use ; Antioxidants - toxicity ; Arachidonic Acid - antagonists & inhibitors ; Benzo(a)pyrene - antagonists & inhibitors ; Benzo(a)pyrene - metabolism ; Biological and medical sciences ; Dermatitis, Contact - etiology ; Dermatitis, Contact - prevention & control ; DNA - metabolism ; Drug Interactions ; Enzyme Induction ; Epidermis - drug effects ; Epidermis - enzymology ; Epidermis - metabolism ; Female ; General pharmacology ; Hyperplasia ; Magnoliopsida ; Medical sciences ; Mice ; Mice, Inbred Strains ; Ornithine Decarboxylase - drug effects ; Ornithine Decarboxylase - metabolism ; Pharmacognosy. Homeopathy. Health food ; Pharmacology. Drug treatments ; Phenanthrenes - therapeutic use ; Plant Extracts - therapeutic use ; Skin - drug effects ; Skin - metabolism ; Skin - pathology ; Skin Neoplasms - chemically induced ; Skin Neoplasms - prevention & control ; Spices ; Tetradecanoylphorbol Acetate - pharmacology ; Triterpenes - therapeutic use ; Tritium ; Ursolic Acid</subject><ispartof>Cancer research (Chicago, Ill.), 1994-02, Vol.54 (3), p.701-708</ispartof><rights>1994 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=3929663$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/8306331$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>MOU-TUAN HUANG</creatorcontrib><creatorcontrib>CHI-TANG HO</creatorcontrib><creatorcontrib>ZHI YUAN WANG</creatorcontrib><creatorcontrib>FERRARO, T</creatorcontrib><creatorcontrib>YOU-RONG LOU</creatorcontrib><creatorcontrib>STAUBER, K</creatorcontrib><creatorcontrib>WEI MA</creatorcontrib><creatorcontrib>GEORGIADIS, C</creatorcontrib><creatorcontrib>LASKIN, J. D</creatorcontrib><creatorcontrib>CONNEY, A. H</creatorcontrib><title>Inhibition of skin tumorigenesis by Rosemary and its constituents carnosol and ursolic acid</title><title>Cancer research (Chicago, Ill.)</title><addtitle>Cancer Res</addtitle><description>A methanol extract of the leaves of the plant Rosmarinus officinalis L. (rosemary) was evaluated for its effects on tumor initiation and promotion in mouse skin. Application of rosemary to mouse skin inhibited the covalent binding of benzo(a)pyrene [B(a)P] to epidermal DNA and inhibited tumor initiation by B(a)P and 7,12-dimethylbenz[a]anthracene (DMBA). Topical application of 20 nmol B(a)P to the backs of mice once weekly for 10 weeks, followed 1 week later by promotion with 15 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) twice weekly for 21 weeks, resulted in the formation of 7.1 tumors per mouse. In a parallel group of animals that were treated topically with 1.2 or 3.6 mg of rosemary 5 min prior to each application of B(a)P, the number of tumors per mouse was decreased by 54 or 64%, respectively. Application of rosemary to mouse skin also inhibited TPA-induced ornithine decarboxylase activity, TPA-induced inflammation, arachidonic acid-induced inflammation, TPA-induced hyperplasia, and TPA-induced tumor promotion. Mice initiated with 200 nmol DMBA and promoted with 5 nmol TPA twice weekly for 19 weeks developed an average of 17.2 skin tumors per mouse. Treatment of the DMBA-initiated mice with 0.4, 1.2, or 3.6 mg of rosemary together with 5 nmol TPA twice weekly for 19 weeks inhibited the number of TPA-induced skin tumors per mouse by 40, 68, or 99%, respectively. Topical application of carnosol or ursolic acid isolated from rosemary inhibited TPA-induced ear inflammation, ornithine decarboxylase activity, and tumor promotion. Topical application of 1, 3, or 10 mumol carnosol together with 5 nmol TPA twice weekly for 20 weeks to the backs of mice previously initiated with DMBA inhibited the number of skin tumors per mouse by 38, 63, or 78%, respectively. Topical application of 0.1, 0.3, 1, or 2 mumol ursolic acid together with 5 nmol TPA twice weekly for 20 weeks to DMBA-initiated mice inhibited the number of tumors per mouse by 45-61%.</description><subject>9,10-Dimethyl-1,2-benzanthracene - antagonists & inhibitors</subject><subject>Abietanes</subject><subject>Animals</subject><subject>Anticarcinogenic Agents - therapeutic use</subject><subject>Antioxidants - toxicity</subject><subject>Arachidonic Acid - antagonists & inhibitors</subject><subject>Benzo(a)pyrene - antagonists & inhibitors</subject><subject>Benzo(a)pyrene - metabolism</subject><subject>Biological and medical sciences</subject><subject>Dermatitis, Contact - etiology</subject><subject>Dermatitis, Contact - prevention & control</subject><subject>DNA - metabolism</subject><subject>Drug Interactions</subject><subject>Enzyme Induction</subject><subject>Epidermis - drug effects</subject><subject>Epidermis - enzymology</subject><subject>Epidermis - metabolism</subject><subject>Female</subject><subject>General pharmacology</subject><subject>Hyperplasia</subject><subject>Magnoliopsida</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Mice, Inbred Strains</subject><subject>Ornithine Decarboxylase - drug effects</subject><subject>Ornithine Decarboxylase - metabolism</subject><subject>Pharmacognosy. Homeopathy. Health food</subject><subject>Pharmacology. Drug treatments</subject><subject>Phenanthrenes - therapeutic use</subject><subject>Plant Extracts - therapeutic use</subject><subject>Skin - drug effects</subject><subject>Skin - metabolism</subject><subject>Skin - pathology</subject><subject>Skin Neoplasms - chemically induced</subject><subject>Skin Neoplasms - prevention & control</subject><subject>Spices</subject><subject>Tetradecanoylphorbol Acetate - pharmacology</subject><subject>Triterpenes - therapeutic use</subject><subject>Tritium</subject><subject>Ursolic Acid</subject><issn>0008-5472</issn><issn>1538-7445</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1994</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNo9j0tLAzEUhYModaz-BCELtwN5TjJLKT4KBUF05aLczCQ2OpOUJLPov3eqxdW5h-9wOPcMVVRyXSsh5DmqCCG6lkKxS3SV89dsJSVygRaak4ZzWqGPddh544uPAUeH87cPuExjTP7TBpt9xuaAX2O2I6QDhtBjXzLuYsjFl8mGo4EUYo7DL53SfPkOQ-f7a3ThYMj25qRL9P748LZ6rjcvT-vV_abesUaVWmoNTLWUasmEZbIxRHJBDOs4EONAMN4yCsoYonswljsmJeGNVNo6QxVfotu_3v1kRttv98kf125PT8787sQhdzC4BKHz-T82t7fNHPwBOxNb-w</recordid><startdate>19940201</startdate><enddate>19940201</enddate><creator>MOU-TUAN HUANG</creator><creator>CHI-TANG HO</creator><creator>ZHI YUAN WANG</creator><creator>FERRARO, T</creator><creator>YOU-RONG LOU</creator><creator>STAUBER, K</creator><creator>WEI MA</creator><creator>GEORGIADIS, C</creator><creator>LASKIN, J. D</creator><creator>CONNEY, A. H</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></search><sort><creationdate>19940201</creationdate><title>Inhibition of skin tumorigenesis by Rosemary and its constituents carnosol and ursolic acid</title><author>MOU-TUAN HUANG ; CHI-TANG HO ; ZHI YUAN WANG ; FERRARO, T ; YOU-RONG LOU ; STAUBER, K ; WEI MA ; GEORGIADIS, C ; LASKIN, J. D ; CONNEY, A. H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-h267t-588a279118524e256b05340b2c3a0bfa423921a7bb08dabe3f255036578efb173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1994</creationdate><topic>9,10-Dimethyl-1,2-benzanthracene - antagonists & inhibitors</topic><topic>Abietanes</topic><topic>Animals</topic><topic>Anticarcinogenic Agents - therapeutic use</topic><topic>Antioxidants - toxicity</topic><topic>Arachidonic Acid - antagonists & inhibitors</topic><topic>Benzo(a)pyrene - antagonists & inhibitors</topic><topic>Benzo(a)pyrene - metabolism</topic><topic>Biological and medical sciences</topic><topic>Dermatitis, Contact - etiology</topic><topic>Dermatitis, Contact - prevention & control</topic><topic>DNA - metabolism</topic><topic>Drug Interactions</topic><topic>Enzyme Induction</topic><topic>Epidermis - drug effects</topic><topic>Epidermis - enzymology</topic><topic>Epidermis - metabolism</topic><topic>Female</topic><topic>General pharmacology</topic><topic>Hyperplasia</topic><topic>Magnoliopsida</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Mice, Inbred Strains</topic><topic>Ornithine Decarboxylase - drug effects</topic><topic>Ornithine Decarboxylase - metabolism</topic><topic>Pharmacognosy. Homeopathy. Health food</topic><topic>Pharmacology. Drug treatments</topic><topic>Phenanthrenes - therapeutic use</topic><topic>Plant Extracts - therapeutic use</topic><topic>Skin - drug effects</topic><topic>Skin - metabolism</topic><topic>Skin - pathology</topic><topic>Skin Neoplasms - chemically induced</topic><topic>Skin Neoplasms - prevention & control</topic><topic>Spices</topic><topic>Tetradecanoylphorbol Acetate - pharmacology</topic><topic>Triterpenes - therapeutic use</topic><topic>Tritium</topic><topic>Ursolic Acid</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>MOU-TUAN HUANG</creatorcontrib><creatorcontrib>CHI-TANG HO</creatorcontrib><creatorcontrib>ZHI YUAN WANG</creatorcontrib><creatorcontrib>FERRARO, T</creatorcontrib><creatorcontrib>YOU-RONG LOU</creatorcontrib><creatorcontrib>STAUBER, K</creatorcontrib><creatorcontrib>WEI MA</creatorcontrib><creatorcontrib>GEORGIADIS, C</creatorcontrib><creatorcontrib>LASKIN, J. D</creatorcontrib><creatorcontrib>CONNEY, A. H</creatorcontrib><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><jtitle>Cancer research (Chicago, Ill.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>MOU-TUAN HUANG</au><au>CHI-TANG HO</au><au>ZHI YUAN WANG</au><au>FERRARO, T</au><au>YOU-RONG LOU</au><au>STAUBER, K</au><au>WEI MA</au><au>GEORGIADIS, C</au><au>LASKIN, J. D</au><au>CONNEY, A. H</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Inhibition of skin tumorigenesis by Rosemary and its constituents carnosol and ursolic acid</atitle><jtitle>Cancer research (Chicago, Ill.)</jtitle><addtitle>Cancer Res</addtitle><date>1994-02-01</date><risdate>1994</risdate><volume>54</volume><issue>3</issue><spage>701</spage><epage>708</epage><pages>701-708</pages><issn>0008-5472</issn><eissn>1538-7445</eissn><coden>CNREA8</coden><abstract>A methanol extract of the leaves of the plant Rosmarinus officinalis L. (rosemary) was evaluated for its effects on tumor initiation and promotion in mouse skin. Application of rosemary to mouse skin inhibited the covalent binding of benzo(a)pyrene [B(a)P] to epidermal DNA and inhibited tumor initiation by B(a)P and 7,12-dimethylbenz[a]anthracene (DMBA). Topical application of 20 nmol B(a)P to the backs of mice once weekly for 10 weeks, followed 1 week later by promotion with 15 nmol 12-O-tetradecanoylphorbol-13-acetate (TPA) twice weekly for 21 weeks, resulted in the formation of 7.1 tumors per mouse. In a parallel group of animals that were treated topically with 1.2 or 3.6 mg of rosemary 5 min prior to each application of B(a)P, the number of tumors per mouse was decreased by 54 or 64%, respectively. Application of rosemary to mouse skin also inhibited TPA-induced ornithine decarboxylase activity, TPA-induced inflammation, arachidonic acid-induced inflammation, TPA-induced hyperplasia, and TPA-induced tumor promotion. Mice initiated with 200 nmol DMBA and promoted with 5 nmol TPA twice weekly for 19 weeks developed an average of 17.2 skin tumors per mouse. Treatment of the DMBA-initiated mice with 0.4, 1.2, or 3.6 mg of rosemary together with 5 nmol TPA twice weekly for 19 weeks inhibited the number of TPA-induced skin tumors per mouse by 40, 68, or 99%, respectively. Topical application of carnosol or ursolic acid isolated from rosemary inhibited TPA-induced ear inflammation, ornithine decarboxylase activity, and tumor promotion. Topical application of 1, 3, or 10 mumol carnosol together with 5 nmol TPA twice weekly for 20 weeks to the backs of mice previously initiated with DMBA inhibited the number of skin tumors per mouse by 38, 63, or 78%, respectively. Topical application of 0.1, 0.3, 1, or 2 mumol ursolic acid together with 5 nmol TPA twice weekly for 20 weeks to DMBA-initiated mice inhibited the number of tumors per mouse by 45-61%.</abstract><cop>Philadelphia, PA</cop><pub>American Association for Cancer Research</pub><pmid>8306331</pmid><tpages>8</tpages></addata></record> |
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| ispartof | Cancer research (Chicago, Ill.), 1994-02, Vol.54 (3), p.701-708 |
| issn | 0008-5472 1538-7445 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; American Association for Cancer Research |
| subjects | 9,10-Dimethyl-1,2-benzanthracene - antagonists & inhibitors Abietanes Animals Anticarcinogenic Agents - therapeutic use Antioxidants - toxicity Arachidonic Acid - antagonists & inhibitors Benzo(a)pyrene - antagonists & inhibitors Benzo(a)pyrene - metabolism Biological and medical sciences Dermatitis, Contact - etiology Dermatitis, Contact - prevention & control DNA - metabolism Drug Interactions Enzyme Induction Epidermis - drug effects Epidermis - enzymology Epidermis - metabolism Female General pharmacology Hyperplasia Magnoliopsida Medical sciences Mice Mice, Inbred Strains Ornithine Decarboxylase - drug effects Ornithine Decarboxylase - metabolism Pharmacognosy. Homeopathy. Health food Pharmacology. Drug treatments Phenanthrenes - therapeutic use Plant Extracts - therapeutic use Skin - drug effects Skin - metabolism Skin - pathology Skin Neoplasms - chemically induced Skin Neoplasms - prevention & control Spices Tetradecanoylphorbol Acetate - pharmacology Triterpenes - therapeutic use Tritium Ursolic Acid |
| title | Inhibition of skin tumorigenesis by Rosemary and its constituents carnosol and ursolic acid |
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