Hormetic dose response to L-ascorbic acid as an anti-cancer drug in colorectal cancer cell lines according to SVCT-2 expression
L -Ascorbic acid (vitamin C, AA) exhibits anti-cancer effects with high-dose treatment through the generation of reactive oxygen species (ROS) and selective damage to cancer cells. The anti-cancer effects of L -ascorbic acid are determined by sodium-dependent vitamin C transporter 2 (SVCT-2), a tran...
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| Veröffentlicht in: | Scientific reports 2018-07, Vol.8 (1), p.11372-9, Article 11372 |
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| creator | Cho, Sungrae Chae, Jin Sung Shin, Hocheol Shin, Yujeong Song, Haeun Kim, Youngwook Yoo, Byong Chul Roh, Kangsan Cho, Seungchan Kil, Eui-joon Byun, Hee-seong Cho, Sang-ho Park, Seyeon Lee, Sukchan Yeom, Chang-Hwan |
| description | L
-Ascorbic acid (vitamin C, AA) exhibits anti-cancer effects with high-dose treatment through the generation of reactive oxygen species (ROS) and selective damage to cancer cells. The anti-cancer effects of
L
-ascorbic acid are determined by sodium-dependent vitamin C transporter 2 (SVCT-2), a transporter of
L
-ascorbic acid. In this study, we demonstrate that
L
-ascorbic acid treatment showed efficient anti-cancer activity in cell lines with high expression levels of SVCT-2 for a gradient concentration of
L
-ascorbic acid from 10 μM −2 mM. However, in low SVCT-2 expressing cell lines, high-dose
L
-ascorbic acid (>1 mM) showed anti-cancer effects but low-dose ( |
| doi_str_mv | 10.1038/s41598-018-29386-7 |
| format | Article |
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-Ascorbic acid (vitamin C, AA) exhibits anti-cancer effects with high-dose treatment through the generation of reactive oxygen species (ROS) and selective damage to cancer cells. The anti-cancer effects of
L
-ascorbic acid are determined by sodium-dependent vitamin C transporter 2 (SVCT-2), a transporter of
L
-ascorbic acid. In this study, we demonstrate that
L
-ascorbic acid treatment showed efficient anti-cancer activity in cell lines with high expression levels of SVCT-2 for a gradient concentration of
L
-ascorbic acid from 10 μM −2 mM. However, in low SVCT-2 expressing cell lines, high-dose
L
-ascorbic acid (>1 mM) showed anti-cancer effects but low-dose (<10 μM) treatment induced cell proliferation. Such conflicting results that depend on the concentration are called a hormetic dose response. A hormetic dose response to low-dose
L
-ascorbic acid was also observed in high SVCT-2 expressing cell lines in the presence of a SVCT family inhibitor. Insufficient uptake of
L
-ascorbic acid in low SVCT-2 expressing cancer cell lines cannot generate sufficient ROS to kill cancer cells, resulting in the hormetic response. Molecular analysis confirmed the increased expression of cancer proliferation markers in the hormetic dose response. These results suggest that
L
-ascorbic exhibits a biphasic effect in cancer cells depending on SVCT-2 expression.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-018-29386-7</identifier><identifier>PMID: 30054560</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/31 ; 14/34 ; 38/77 ; 631/67/1059 ; 631/67/1059/602 ; 82/1 ; 82/51 ; Acids ; Ascorbic acid ; Cell proliferation ; Colorectal cancer ; Colorectal carcinoma ; Humanities and Social Sciences ; multidisciplinary ; Reactive oxygen species ; Science ; Science (multidisciplinary) ; Sodium ; Tumor cell lines ; Vitamin C</subject><ispartof>Scientific reports, 2018-07, Vol.8 (1), p.11372-9, Article 11372</ispartof><rights>The Author(s) 2018</rights><rights>2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c474t-780943951a090771359559d8bd0d037381acdf30d584cd00b40a201dfecb4a003</citedby><cites>FETCH-LOGICAL-c474t-780943951a090771359559d8bd0d037381acdf30d584cd00b40a201dfecb4a003</cites><orcidid>0000-0002-9964-0176</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063950/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6063950/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30054560$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Cho, Sungrae</creatorcontrib><creatorcontrib>Chae, Jin Sung</creatorcontrib><creatorcontrib>Shin, Hocheol</creatorcontrib><creatorcontrib>Shin, Yujeong</creatorcontrib><creatorcontrib>Song, Haeun</creatorcontrib><creatorcontrib>Kim, Youngwook</creatorcontrib><creatorcontrib>Yoo, Byong Chul</creatorcontrib><creatorcontrib>Roh, Kangsan</creatorcontrib><creatorcontrib>Cho, Seungchan</creatorcontrib><creatorcontrib>Kil, Eui-joon</creatorcontrib><creatorcontrib>Byun, Hee-seong</creatorcontrib><creatorcontrib>Cho, Sang-ho</creatorcontrib><creatorcontrib>Park, Seyeon</creatorcontrib><creatorcontrib>Lee, Sukchan</creatorcontrib><creatorcontrib>Yeom, Chang-Hwan</creatorcontrib><title>Hormetic dose response to L-ascorbic acid as an anti-cancer drug in colorectal cancer cell lines according to SVCT-2 expression</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>L
-Ascorbic acid (vitamin C, AA) exhibits anti-cancer effects with high-dose treatment through the generation of reactive oxygen species (ROS) and selective damage to cancer cells. The anti-cancer effects of
L
-ascorbic acid are determined by sodium-dependent vitamin C transporter 2 (SVCT-2), a transporter of
L
-ascorbic acid. In this study, we demonstrate that
L
-ascorbic acid treatment showed efficient anti-cancer activity in cell lines with high expression levels of SVCT-2 for a gradient concentration of
L
-ascorbic acid from 10 μM −2 mM. However, in low SVCT-2 expressing cell lines, high-dose
L
-ascorbic acid (>1 mM) showed anti-cancer effects but low-dose (<10 μM) treatment induced cell proliferation. Such conflicting results that depend on the concentration are called a hormetic dose response. A hormetic dose response to low-dose
L
-ascorbic acid was also observed in high SVCT-2 expressing cell lines in the presence of a SVCT family inhibitor. Insufficient uptake of
L
-ascorbic acid in low SVCT-2 expressing cancer cell lines cannot generate sufficient ROS to kill cancer cells, resulting in the hormetic response. Molecular analysis confirmed the increased expression of cancer proliferation markers in the hormetic dose response. These results suggest that
L
-ascorbic exhibits a biphasic effect in cancer cells depending on SVCT-2 expression.</description><subject>13/31</subject><subject>14/34</subject><subject>38/77</subject><subject>631/67/1059</subject><subject>631/67/1059/602</subject><subject>82/1</subject><subject>82/51</subject><subject>Acids</subject><subject>Ascorbic acid</subject><subject>Cell proliferation</subject><subject>Colorectal cancer</subject><subject>Colorectal carcinoma</subject><subject>Humanities and Social Sciences</subject><subject>multidisciplinary</subject><subject>Reactive oxygen species</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Sodium</subject><subject>Tumor cell lines</subject><subject>Vitamin 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China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Cho, Sungrae</au><au>Chae, Jin Sung</au><au>Shin, Hocheol</au><au>Shin, Yujeong</au><au>Song, Haeun</au><au>Kim, Youngwook</au><au>Yoo, Byong Chul</au><au>Roh, Kangsan</au><au>Cho, Seungchan</au><au>Kil, Eui-joon</au><au>Byun, Hee-seong</au><au>Cho, Sang-ho</au><au>Park, Seyeon</au><au>Lee, Sukchan</au><au>Yeom, Chang-Hwan</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Hormetic dose response to L-ascorbic acid as an anti-cancer drug in colorectal cancer cell lines according to SVCT-2 expression</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2018-07-27</date><risdate>2018</risdate><volume>8</volume><issue>1</issue><spage>11372</spage><epage>9</epage><pages>11372-9</pages><artnum>11372</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>L
-Ascorbic acid (vitamin C, AA) exhibits anti-cancer effects with high-dose treatment through the generation of reactive oxygen species (ROS) and selective damage to cancer cells. The anti-cancer effects of
L
-ascorbic acid are determined by sodium-dependent vitamin C transporter 2 (SVCT-2), a transporter of
L
-ascorbic acid. In this study, we demonstrate that
L
-ascorbic acid treatment showed efficient anti-cancer activity in cell lines with high expression levels of SVCT-2 for a gradient concentration of
L
-ascorbic acid from 10 μM −2 mM. However, in low SVCT-2 expressing cell lines, high-dose
L
-ascorbic acid (>1 mM) showed anti-cancer effects but low-dose (<10 μM) treatment induced cell proliferation. Such conflicting results that depend on the concentration are called a hormetic dose response. A hormetic dose response to low-dose
L
-ascorbic acid was also observed in high SVCT-2 expressing cell lines in the presence of a SVCT family inhibitor. Insufficient uptake of
L
-ascorbic acid in low SVCT-2 expressing cancer cell lines cannot generate sufficient ROS to kill cancer cells, resulting in the hormetic response. Molecular analysis confirmed the increased expression of cancer proliferation markers in the hormetic dose response. These results suggest that
L
-ascorbic exhibits a biphasic effect in cancer cells depending on SVCT-2 expression.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>30054560</pmid><doi>10.1038/s41598-018-29386-7</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-9964-0176</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Scientific reports, 2018-07, Vol.8 (1), p.11372-9, Article 11372 |
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| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6063950 |
| source | DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 13/31 14/34 38/77 631/67/1059 631/67/1059/602 82/1 82/51 Acids Ascorbic acid Cell proliferation Colorectal cancer Colorectal carcinoma Humanities and Social Sciences multidisciplinary Reactive oxygen species Science Science (multidisciplinary) Sodium Tumor cell lines Vitamin C |
| title | Hormetic dose response to L-ascorbic acid as an anti-cancer drug in colorectal cancer cell lines according to SVCT-2 expression |
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