Anti-tumor Effects of All-trans Retinoic Acid are Enhanced by Genistein
The effects of all-trans retinoic acid (ATRA) on cancer are complex. ATRA has anti-cancer effects as it promotes cancer cell differentiation. However, ATRA also up-regulates expression of vascular endothelial growth factor (VEGF) in cancer cells, which leads to angiogenesis and can, thus, facilitate...
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| Veröffentlicht in: | Cell biochemistry and biophysics 2012, Vol.62 (1), p.177-184 |
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| creator | Zhou, Ren-Jie Yang, Xue-Qin Wang, Dong Zhou, Qian Xia, Lei Li, Meng-Xia Zeng, Lin-Li Wang, Ge Yang, Zhen-Zhou |
| description | The effects of all-trans retinoic acid (ATRA) on cancer are complex. ATRA has anti-cancer effects as it promotes cancer cell differentiation. However, ATRA also up-regulates expression of vascular endothelial growth factor (VEGF) in cancer cells, which leads to angiogenesis and can, thus, facilitate cancer growth. Genistein, a crucial non-nutrient component in soybean, exhibits anti-cancer effects by inhibiting protein tyrosine kinase that is involved in up-regulation of VEGF. We hypothesized that genistein, applied simultaneously with ATRA, would counter its undesired angiogenic effects and, thus, enhance the anti-cancer effects of ATRA. The purpose of this study was to document potential synergistic effects of genistein and ATRA in A549 lung adenocarcinoma cells. We further explored the role of genistein on countering the ATRA-induced VEGF expression. We demonstrate that genistein enhances the ATRA-induced growth inhibition of A549 cells by promoting apoptosis. Further, the combined use of ATRA and genistein leads to cancer cell arrest in G0/G1 and G2/M cell cycle phases. Finally, expression of VEGF (both mRNA and protein) was diminished in A549 cells exposed to both ATRA and genistein. In conclusion, our results demonstrate that genistein effectively enhances anti-cancer effects of ATRA, particularly, by countering the ATRA-induced up-regulation of VEGF. Our study provides an experimental basis for combined use of ATRA and genistein in the treatment of lung cancer. |
| doi_str_mv | 10.1007/s12013-011-9279-0 |
| format | Article |
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ATRA has anti-cancer effects as it promotes cancer cell differentiation. However, ATRA also up-regulates expression of vascular endothelial growth factor (VEGF) in cancer cells, which leads to angiogenesis and can, thus, facilitate cancer growth. Genistein, a crucial non-nutrient component in soybean, exhibits anti-cancer effects by inhibiting protein tyrosine kinase that is involved in up-regulation of VEGF. We hypothesized that genistein, applied simultaneously with ATRA, would counter its undesired angiogenic effects and, thus, enhance the anti-cancer effects of ATRA. The purpose of this study was to document potential synergistic effects of genistein and ATRA in A549 lung adenocarcinoma cells. We further explored the role of genistein on countering the ATRA-induced VEGF expression. We demonstrate that genistein enhances the ATRA-induced growth inhibition of A549 cells by promoting apoptosis. Further, the combined use of ATRA and genistein leads to cancer cell arrest in G0/G1 and G2/M cell cycle phases. Finally, expression of VEGF (both mRNA and protein) was diminished in A549 cells exposed to both ATRA and genistein. In conclusion, our results demonstrate that genistein effectively enhances anti-cancer effects of ATRA, particularly, by countering the ATRA-induced up-regulation of VEGF. Our study provides an experimental basis for combined use of ATRA and genistein in the treatment of lung cancer.</description><identifier>ISSN: 1085-9195</identifier><identifier>EISSN: 1559-0283</identifier><identifier>DOI: 10.1007/s12013-011-9279-0</identifier><identifier>PMID: 21898109</identifier><language>eng</language><publisher>New York: Humana Press Inc</publisher><subject>Adenocarcinoma - pathology ; Antineoplastic Agents - pharmacology ; Apoptosis - drug effects ; Biochemistry ; Biological and Medical Physics ; Biomedical and Life Sciences ; Biophysics ; Biotechnology ; Cell Biology ; Cell Cycle - drug effects ; Cell differentiation ; Cell Line, Tumor ; Drug Synergism ; G1 Phase Cell Cycle Checkpoints ; G2 Phase Cell Cycle Checkpoints ; Genistein - pharmacology ; Humans ; Life Sciences ; Lung cancer ; Lung Neoplasms - pathology ; M Phase Cell Cycle Checkpoints ; Original Paper ; Pharmacology/Toxicology ; Soybeans ; Synergistic effect ; Tretinoin - pharmacology ; Up-Regulation - drug effects ; Vascular Endothelial Growth Factor A - genetics ; Vascular Endothelial Growth Factor A - metabolism</subject><ispartof>Cell biochemistry and biophysics, 2012, Vol.62 (1), p.177-184</ispartof><rights>Springer Science+Business Media, LLC 2011</rights><rights>Springer Science+Business Media, LLC 2012</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c370t-f3127cc021da7dfa58ab038ca27a4f1a2aea360780af5fce3009d9f1fca680273</citedby><cites>FETCH-LOGICAL-c370t-f3127cc021da7dfa58ab038ca27a4f1a2aea360780af5fce3009d9f1fca680273</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s12013-011-9279-0$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s12013-011-9279-0$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21898109$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Ren-Jie</creatorcontrib><creatorcontrib>Yang, Xue-Qin</creatorcontrib><creatorcontrib>Wang, Dong</creatorcontrib><creatorcontrib>Zhou, Qian</creatorcontrib><creatorcontrib>Xia, Lei</creatorcontrib><creatorcontrib>Li, Meng-Xia</creatorcontrib><creatorcontrib>Zeng, Lin-Li</creatorcontrib><creatorcontrib>Wang, Ge</creatorcontrib><creatorcontrib>Yang, Zhen-Zhou</creatorcontrib><title>Anti-tumor Effects of All-trans Retinoic Acid are Enhanced by Genistein</title><title>Cell biochemistry and biophysics</title><addtitle>Cell Biochem Biophys</addtitle><addtitle>Cell Biochem Biophys</addtitle><description>The effects of all-trans retinoic acid (ATRA) on cancer are complex. ATRA has anti-cancer effects as it promotes cancer cell differentiation. However, ATRA also up-regulates expression of vascular endothelial growth factor (VEGF) in cancer cells, which leads to angiogenesis and can, thus, facilitate cancer growth. Genistein, a crucial non-nutrient component in soybean, exhibits anti-cancer effects by inhibiting protein tyrosine kinase that is involved in up-regulation of VEGF. We hypothesized that genistein, applied simultaneously with ATRA, would counter its undesired angiogenic effects and, thus, enhance the anti-cancer effects of ATRA. The purpose of this study was to document potential synergistic effects of genistein and ATRA in A549 lung adenocarcinoma cells. We further explored the role of genistein on countering the ATRA-induced VEGF expression. We demonstrate that genistein enhances the ATRA-induced growth inhibition of A549 cells by promoting apoptosis. Further, the combined use of ATRA and genistein leads to cancer cell arrest in G0/G1 and G2/M cell cycle phases. Finally, expression of VEGF (both mRNA and protein) was diminished in A549 cells exposed to both ATRA and genistein. In conclusion, our results demonstrate that genistein effectively enhances anti-cancer effects of ATRA, particularly, by countering the ATRA-induced up-regulation of VEGF. Our study provides an experimental basis for combined use of ATRA and genistein in the treatment of lung cancer.</description><subject>Adenocarcinoma - pathology</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Biochemistry</subject><subject>Biological and Medical Physics</subject><subject>Biomedical and Life Sciences</subject><subject>Biophysics</subject><subject>Biotechnology</subject><subject>Cell Biology</subject><subject>Cell Cycle - drug effects</subject><subject>Cell differentiation</subject><subject>Cell Line, Tumor</subject><subject>Drug Synergism</subject><subject>G1 Phase Cell Cycle Checkpoints</subject><subject>G2 Phase Cell Cycle Checkpoints</subject><subject>Genistein - pharmacology</subject><subject>Humans</subject><subject>Life Sciences</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - pathology</subject><subject>M Phase Cell Cycle Checkpoints</subject><subject>Original Paper</subject><subject>Pharmacology/Toxicology</subject><subject>Soybeans</subject><subject>Synergistic effect</subject><subject>Tretinoin - pharmacology</subject><subject>Up-Regulation - drug effects</subject><subject>Vascular Endothelial Growth Factor A - genetics</subject><subject>Vascular Endothelial Growth Factor A - metabolism</subject><issn>1085-9195</issn><issn>1559-0283</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kMFKAzEQhoMoVqsP4EWCF0_RmaS7mxxLqVUoCKLnkGYT3bKbrcnuoW_vllYFwdMMzDf_DB8hVwh3CFDcJ-SAggEiU7xQDI7IGWbZ0HApjoceZMYUqmxEzlNaA3AOk8kpGXGUSiKoM7KYhq5iXd-0kc69d7ZLtPV0WtesiyYk-uK6KrSVpVNbldRER-fhwwTrSrra0oULVepcFS7IiTd1cpeHOiZvD_PX2SNbPi-eZtMls6KAjnmBvLAWOJamKL3JpFmBkNbwwkw8Gm6cETkUEozPvHUCQJXKo7cml8ALMSa3-9xNbD97lzrdVMm6ujbBtX3SCrOcyxz4QN78IddtH8Pw3A6CDIXaQbiHbGxTis7rTawaE7caQe8c671jPTjWO8cahp3rQ3C_alz5s_EtdQD4HkjDKLy7-Hv5_9Qv-cmFQg</recordid><startdate>2012</startdate><enddate>2012</enddate><creator>Zhou, Ren-Jie</creator><creator>Yang, Xue-Qin</creator><creator>Wang, Dong</creator><creator>Zhou, Qian</creator><creator>Xia, Lei</creator><creator>Li, Meng-Xia</creator><creator>Zeng, Lin-Li</creator><creator>Wang, Ge</creator><creator>Yang, Zhen-Zhou</creator><general>Humana Press Inc</general><general>Springer Nature B.V</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>3V.</scope><scope>7QL</scope><scope>7T5</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>2012</creationdate><title>Anti-tumor Effects of All-trans Retinoic Acid are Enhanced by Genistein</title><author>Zhou, Ren-Jie ; Yang, Xue-Qin ; Wang, Dong ; Zhou, Qian ; Xia, Lei ; Li, Meng-Xia ; Zeng, Lin-Li ; Wang, Ge ; Yang, Zhen-Zhou</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c370t-f3127cc021da7dfa58ab038ca27a4f1a2aea360780af5fce3009d9f1fca680273</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Adenocarcinoma - 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Academic</collection><jtitle>Cell biochemistry and biophysics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Ren-Jie</au><au>Yang, Xue-Qin</au><au>Wang, Dong</au><au>Zhou, Qian</au><au>Xia, Lei</au><au>Li, Meng-Xia</au><au>Zeng, Lin-Li</au><au>Wang, Ge</au><au>Yang, Zhen-Zhou</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Anti-tumor Effects of All-trans Retinoic Acid are Enhanced by Genistein</atitle><jtitle>Cell biochemistry and biophysics</jtitle><stitle>Cell Biochem Biophys</stitle><addtitle>Cell Biochem Biophys</addtitle><date>2012</date><risdate>2012</risdate><volume>62</volume><issue>1</issue><spage>177</spage><epage>184</epage><pages>177-184</pages><issn>1085-9195</issn><eissn>1559-0283</eissn><abstract>The effects of all-trans retinoic acid (ATRA) on cancer are complex. ATRA has anti-cancer effects as it promotes cancer cell differentiation. However, ATRA also up-regulates expression of vascular endothelial growth factor (VEGF) in cancer cells, which leads to angiogenesis and can, thus, facilitate cancer growth. Genistein, a crucial non-nutrient component in soybean, exhibits anti-cancer effects by inhibiting protein tyrosine kinase that is involved in up-regulation of VEGF. We hypothesized that genistein, applied simultaneously with ATRA, would counter its undesired angiogenic effects and, thus, enhance the anti-cancer effects of ATRA. The purpose of this study was to document potential synergistic effects of genistein and ATRA in A549 lung adenocarcinoma cells. We further explored the role of genistein on countering the ATRA-induced VEGF expression. We demonstrate that genistein enhances the ATRA-induced growth inhibition of A549 cells by promoting apoptosis. Further, the combined use of ATRA and genistein leads to cancer cell arrest in G0/G1 and G2/M cell cycle phases. Finally, expression of VEGF (both mRNA and protein) was diminished in A549 cells exposed to both ATRA and genistein. In conclusion, our results demonstrate that genistein effectively enhances anti-cancer effects of ATRA, particularly, by countering the ATRA-induced up-regulation of VEGF. Our study provides an experimental basis for combined use of ATRA and genistein in the treatment of lung cancer.</abstract><cop>New York</cop><pub>Humana Press Inc</pub><pmid>21898109</pmid><doi>10.1007/s12013-011-9279-0</doi><tpages>8</tpages></addata></record> |
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| subjects | Adenocarcinoma - pathology Antineoplastic Agents - pharmacology Apoptosis - drug effects Biochemistry Biological and Medical Physics Biomedical and Life Sciences Biophysics Biotechnology Cell Biology Cell Cycle - drug effects Cell differentiation Cell Line, Tumor Drug Synergism G1 Phase Cell Cycle Checkpoints G2 Phase Cell Cycle Checkpoints Genistein - pharmacology Humans Life Sciences Lung cancer Lung Neoplasms - pathology M Phase Cell Cycle Checkpoints Original Paper Pharmacology/Toxicology Soybeans Synergistic effect Tretinoin - pharmacology Up-Regulation - drug effects Vascular Endothelial Growth Factor A - genetics Vascular Endothelial Growth Factor A - metabolism |
| title | Anti-tumor Effects of All-trans Retinoic Acid are Enhanced by Genistein |
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