Topical Applications of Caffeine or (-)-Epigallocatechin Gallate (EGCG) Inhibit Carcinogenesis and Selectively Increase Apoptosis in UVB-Induced Skin Tumors in Mice
SKH-1 hairless mice were irradiated with ultraviolet B (UVB) twice weekly for 20 weeks. These tumor-free mice, which had a high risk of developing skin tumors during the next several months, were then treated topically with caffeine (6.2 µmol) or (-)-epigallocatechin gallate (EGCG; 6.5 µmol) once a...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 2002-09, Vol.99 (19), p.12455-12460 |
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| container_title | Proceedings of the National Academy of Sciences - PNAS |
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| creator | Lu, Yao-Ping Lou, You-Rong Xie, Jian-Guo Peng, Qing-Yun Liao, Jie Yang, Chung S. Huang, Mou-Tuan Conney, Allan H. |
| description | SKH-1 hairless mice were irradiated with ultraviolet B (UVB) twice weekly for 20 weeks. These tumor-free mice, which had a high risk of developing skin tumors during the next several months, were then treated topically with caffeine (6.2 µmol) or (-)-epigallocatechin gallate (EGCG; 6.5 µmol) once a day 5 days a week for 18 weeks in the absence of further treatment with UVB. Topical applications of caffeine to these mice decreased the number of nonmalignant and malignant skin tumors per mouse by 44% and 72%, respectively. Topical applications of EGCG decreased the number of nonmalignant and malignant tumors per mouse by 55% and 66%, respectively. Immunohistochemical analysis showed that topical applications of caffeine or EGCG increased apoptosis as measured by the number of caspase 3-positive cells in nonmalignant skin tumors by 87% or 72%, respectively, and in squamous cell carcinomas by 92% or 56%, respectively, but there was no effect on apoptosis in nontumor areas of the epidermis. Topical applications of caffeine or EGCG had a small inhibitory effect on proliferation in nonmalignant tumors as measured by BrdUrd labeling (16-22%), and there was also a similar, but nonsignificant, inhibitory effect on proliferation in malignant tumors. The results suggest a need for further studies to determine whether topical applications of caffeine or EGCG can inhibit sunlight-induced skin cancer in humans. |
| doi_str_mv | 10.1073/pnas.182429899 |
| format | Article |
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These tumor-free mice, which had a high risk of developing skin tumors during the next several months, were then treated topically with caffeine (6.2 µmol) or (-)-epigallocatechin gallate (EGCG; 6.5 µmol) once a day 5 days a week for 18 weeks in the absence of further treatment with UVB. Topical applications of caffeine to these mice decreased the number of nonmalignant and malignant skin tumors per mouse by 44% and 72%, respectively. Topical applications of EGCG decreased the number of nonmalignant and malignant tumors per mouse by 55% and 66%, respectively. Immunohistochemical analysis showed that topical applications of caffeine or EGCG increased apoptosis as measured by the number of caspase 3-positive cells in nonmalignant skin tumors by 87% or 72%, respectively, and in squamous cell carcinomas by 92% or 56%, respectively, but there was no effect on apoptosis in nontumor areas of the epidermis. Topical applications of caffeine or EGCG had a small inhibitory effect on proliferation in nonmalignant tumors as measured by BrdUrd labeling (16-22%), and there was also a similar, but nonsignificant, inhibitory effect on proliferation in malignant tumors. The results suggest a need for further studies to determine whether topical applications of caffeine or EGCG can inhibit sunlight-induced skin cancer in humans.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.182429899</identifier><identifier>PMID: 12205293</identifier><language>eng</language><publisher>United States: National Academy of Sciences</publisher><subject>Administration, Topical ; Animals ; Apoptosis ; Apoptosis - drug effects ; Biological Sciences ; Bromodeoxyuridine - metabolism ; Caffeine - administration & dosage ; Cancer ; Carcinogenesis ; Caspase 3 ; Caspases - metabolism ; Catechin - administration & dosage ; Catechin - analogs & derivatives ; Cell lines ; Cell membranes ; Female ; Mice ; Mice, Hairless ; Neoplasms, Radiation-Induced - etiology ; Neoplasms, Radiation-Induced - metabolism ; Neoplasms, Radiation-Induced - pathology ; Neoplasms, Radiation-Induced - prevention & control ; Skin cancers ; Skin Neoplasms - etiology ; Skin Neoplasms - metabolism ; Skin Neoplasms - pathology ; Skin Neoplasms - prevention & control ; Squamous cell carcinoma ; Tea - chemistry ; Topical application ; Tumors ; Ultraviolet Rays - adverse effects</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 2002-09, Vol.99 (19), p.12455-12460</ispartof><rights>Copyright 1993-2002 National Academy of Sciences of the United States of America</rights><rights>Copyright © 2002, The National Academy of Sciences 2002</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c560t-bfaf98c824f2e62b705f6ecbf2ac000fbea3e573480be73048040de0e599e1553</citedby><cites>FETCH-LOGICAL-c560t-bfaf98c824f2e62b705f6ecbf2ac000fbea3e573480be73048040de0e599e1553</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/99/19.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/3073236$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/3073236$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,724,777,781,800,882,27905,27906,53772,53774,57998,58231</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12205293$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lu, Yao-Ping</creatorcontrib><creatorcontrib>Lou, You-Rong</creatorcontrib><creatorcontrib>Xie, Jian-Guo</creatorcontrib><creatorcontrib>Peng, Qing-Yun</creatorcontrib><creatorcontrib>Liao, Jie</creatorcontrib><creatorcontrib>Yang, Chung S.</creatorcontrib><creatorcontrib>Huang, Mou-Tuan</creatorcontrib><creatorcontrib>Conney, Allan H.</creatorcontrib><title>Topical Applications of Caffeine or (-)-Epigallocatechin Gallate (EGCG) Inhibit Carcinogenesis and Selectively Increase Apoptosis in UVB-Induced Skin Tumors in Mice</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>SKH-1 hairless mice were irradiated with ultraviolet B (UVB) twice weekly for 20 weeks. These tumor-free mice, which had a high risk of developing skin tumors during the next several months, were then treated topically with caffeine (6.2 µmol) or (-)-epigallocatechin gallate (EGCG; 6.5 µmol) once a day 5 days a week for 18 weeks in the absence of further treatment with UVB. Topical applications of caffeine to these mice decreased the number of nonmalignant and malignant skin tumors per mouse by 44% and 72%, respectively. Topical applications of EGCG decreased the number of nonmalignant and malignant tumors per mouse by 55% and 66%, respectively. Immunohistochemical analysis showed that topical applications of caffeine or EGCG increased apoptosis as measured by the number of caspase 3-positive cells in nonmalignant skin tumors by 87% or 72%, respectively, and in squamous cell carcinomas by 92% or 56%, respectively, but there was no effect on apoptosis in nontumor areas of the epidermis. Topical applications of caffeine or EGCG had a small inhibitory effect on proliferation in nonmalignant tumors as measured by BrdUrd labeling (16-22%), and there was also a similar, but nonsignificant, inhibitory effect on proliferation in malignant tumors. The results suggest a need for further studies to determine whether topical applications of caffeine or EGCG can inhibit sunlight-induced skin cancer in humans.</description><subject>Administration, Topical</subject><subject>Animals</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Biological Sciences</subject><subject>Bromodeoxyuridine - metabolism</subject><subject>Caffeine - administration & dosage</subject><subject>Cancer</subject><subject>Carcinogenesis</subject><subject>Caspase 3</subject><subject>Caspases - metabolism</subject><subject>Catechin - administration & dosage</subject><subject>Catechin - analogs & derivatives</subject><subject>Cell lines</subject><subject>Cell membranes</subject><subject>Female</subject><subject>Mice</subject><subject>Mice, Hairless</subject><subject>Neoplasms, Radiation-Induced - etiology</subject><subject>Neoplasms, Radiation-Induced - metabolism</subject><subject>Neoplasms, Radiation-Induced - pathology</subject><subject>Neoplasms, Radiation-Induced - prevention & control</subject><subject>Skin cancers</subject><subject>Skin Neoplasms - etiology</subject><subject>Skin Neoplasms - metabolism</subject><subject>Skin Neoplasms - pathology</subject><subject>Skin Neoplasms - prevention & control</subject><subject>Squamous cell carcinoma</subject><subject>Tea - chemistry</subject><subject>Topical application</subject><subject>Tumors</subject><subject>Ultraviolet Rays - adverse effects</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kcGO0zAQhiMEYrsLV04IckLdQ4rtxEl84LBUpVRaxIEuV8txx62X1A52stp9Hx6UCS0FLkiWZuz5_pnxTJK8oGRGSZW_7ZyKM1qzgolaiEfJhBJBs7IQ5HEyIYRVWV2w4iw5j_GWECJ4TZ4mZ5QxwpnIJ8mPte-sVm161XUtOr31LqbepHNlDFgHqQ_pNLvMFp3dqrb1iIDeWZcu8YZ-Ol0s58vLdOV2trE96oK2zm_BQbQxVW6TfoEWdG_voH1ATAdQEbCe73o_Ipjr5uv7bOU2gwakv-HDetj78Cv0yWp4ljwxqo3w_GgvkpsPi_X8Y3b9ebmaX11nmpekzxqjjKg1DsMwKFlTEW5K0I1hSuPfTQMqB17lRU0aqHKCtiAbIMCFAMp5fpG8O-TthmYPGw2uD6qVXbB7FR6kV1b-G3F2J7f-TlImirJE_ZujPvjvA8Re7m3UgHNy4IcoaV3UPK_GQrMDqIOPMYA51aBEjnuV417laa8oePV3Z3_w4yIRmB6BUfg7LISkeFjBuTRD2_Zw3yP6-v8oEi8PxG3sfTghOTbG8jL_CWppwv4</recordid><startdate>20020917</startdate><enddate>20020917</enddate><creator>Lu, Yao-Ping</creator><creator>Lou, You-Rong</creator><creator>Xie, Jian-Guo</creator><creator>Peng, Qing-Yun</creator><creator>Liao, Jie</creator><creator>Yang, Chung S.</creator><creator>Huang, Mou-Tuan</creator><creator>Conney, Allan H.</creator><general>National Academy of Sciences</general><general>National Acad Sciences</general><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>7U7</scope><scope>C1K</scope><scope>5PM</scope></search><sort><creationdate>20020917</creationdate><title>Topical Applications of Caffeine or (-)-Epigallocatechin Gallate (EGCG) Inhibit Carcinogenesis and Selectively Increase Apoptosis in UVB-Induced Skin Tumors in Mice</title><author>Lu, Yao-Ping ; Lou, You-Rong ; Xie, Jian-Guo ; Peng, Qing-Yun ; Liao, Jie ; Yang, Chung S. ; Huang, Mou-Tuan ; Conney, Allan H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c560t-bfaf98c824f2e62b705f6ecbf2ac000fbea3e573480be73048040de0e599e1553</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Administration, Topical</topic><topic>Animals</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Biological Sciences</topic><topic>Bromodeoxyuridine - metabolism</topic><topic>Caffeine - administration & dosage</topic><topic>Cancer</topic><topic>Carcinogenesis</topic><topic>Caspase 3</topic><topic>Caspases - metabolism</topic><topic>Catechin - administration & dosage</topic><topic>Catechin - analogs & derivatives</topic><topic>Cell lines</topic><topic>Cell membranes</topic><topic>Female</topic><topic>Mice</topic><topic>Mice, Hairless</topic><topic>Neoplasms, Radiation-Induced - etiology</topic><topic>Neoplasms, Radiation-Induced - metabolism</topic><topic>Neoplasms, Radiation-Induced - pathology</topic><topic>Neoplasms, Radiation-Induced - prevention & control</topic><topic>Skin cancers</topic><topic>Skin Neoplasms - etiology</topic><topic>Skin Neoplasms - metabolism</topic><topic>Skin Neoplasms - pathology</topic><topic>Skin Neoplasms - prevention & control</topic><topic>Squamous cell carcinoma</topic><topic>Tea - chemistry</topic><topic>Topical application</topic><topic>Tumors</topic><topic>Ultraviolet Rays - adverse effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lu, Yao-Ping</creatorcontrib><creatorcontrib>Lou, You-Rong</creatorcontrib><creatorcontrib>Xie, Jian-Guo</creatorcontrib><creatorcontrib>Peng, Qing-Yun</creatorcontrib><creatorcontrib>Liao, Jie</creatorcontrib><creatorcontrib>Yang, Chung S.</creatorcontrib><creatorcontrib>Huang, Mou-Tuan</creatorcontrib><creatorcontrib>Conney, Allan H.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, Yao-Ping</au><au>Lou, You-Rong</au><au>Xie, Jian-Guo</au><au>Peng, Qing-Yun</au><au>Liao, Jie</au><au>Yang, Chung S.</au><au>Huang, Mou-Tuan</au><au>Conney, Allan H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Topical Applications of Caffeine or (-)-Epigallocatechin Gallate (EGCG) Inhibit Carcinogenesis and Selectively Increase Apoptosis in UVB-Induced Skin Tumors in Mice</atitle><jtitle>Proceedings of the National Academy of Sciences - PNAS</jtitle><addtitle>Proc Natl Acad Sci U S A</addtitle><date>2002-09-17</date><risdate>2002</risdate><volume>99</volume><issue>19</issue><spage>12455</spage><epage>12460</epage><pages>12455-12460</pages><issn>0027-8424</issn><eissn>1091-6490</eissn><abstract>SKH-1 hairless mice were irradiated with ultraviolet B (UVB) twice weekly for 20 weeks. These tumor-free mice, which had a high risk of developing skin tumors during the next several months, were then treated topically with caffeine (6.2 µmol) or (-)-epigallocatechin gallate (EGCG; 6.5 µmol) once a day 5 days a week for 18 weeks in the absence of further treatment with UVB. Topical applications of caffeine to these mice decreased the number of nonmalignant and malignant skin tumors per mouse by 44% and 72%, respectively. Topical applications of EGCG decreased the number of nonmalignant and malignant tumors per mouse by 55% and 66%, respectively. Immunohistochemical analysis showed that topical applications of caffeine or EGCG increased apoptosis as measured by the number of caspase 3-positive cells in nonmalignant skin tumors by 87% or 72%, respectively, and in squamous cell carcinomas by 92% or 56%, respectively, but there was no effect on apoptosis in nontumor areas of the epidermis. Topical applications of caffeine or EGCG had a small inhibitory effect on proliferation in nonmalignant tumors as measured by BrdUrd labeling (16-22%), and there was also a similar, but nonsignificant, inhibitory effect on proliferation in malignant tumors. The results suggest a need for further studies to determine whether topical applications of caffeine or EGCG can inhibit sunlight-induced skin cancer in humans.</abstract><cop>United States</cop><pub>National Academy of Sciences</pub><pmid>12205293</pmid><doi>10.1073/pnas.182429899</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Administration, Topical Animals Apoptosis Apoptosis - drug effects Biological Sciences Bromodeoxyuridine - metabolism Caffeine - administration & dosage Cancer Carcinogenesis Caspase 3 Caspases - metabolism Catechin - administration & dosage Catechin - analogs & derivatives Cell lines Cell membranes Female Mice Mice, Hairless Neoplasms, Radiation-Induced - etiology Neoplasms, Radiation-Induced - metabolism Neoplasms, Radiation-Induced - pathology Neoplasms, Radiation-Induced - prevention & control Skin cancers Skin Neoplasms - etiology Skin Neoplasms - metabolism Skin Neoplasms - pathology Skin Neoplasms - prevention & control Squamous cell carcinoma Tea - chemistry Topical application Tumors Ultraviolet Rays - adverse effects |
| title | Topical Applications of Caffeine or (-)-Epigallocatechin Gallate (EGCG) Inhibit Carcinogenesis and Selectively Increase Apoptosis in UVB-Induced Skin Tumors in Mice |
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