Artesunate Enhances the Cytotoxicity of 5-Aminolevulinic Acid-Based Sonodynamic Therapy against Mouse Mammary Tumor Cells In Vitro
Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound (US) and a sonosensitizer agent. 5-Aminolevulinic acid (5-ALA) has been used as a sonodynamic sensitizer for cancer treatment. However, studies have shown that 5-ALA-based SDT has limited efficacy against malig...
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| Veröffentlicht in: | Molecules (Basel, Switzerland) Switzerland), 2017-03, Vol.22 (4), p.533 |
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| creator | Osaki, Tomohiro Uto, Yoshihiro Ishizuka, Masahiro Tanaka, Tohru Yamanaka, Nobuyasu Kurahashi, Tsukasa Azuma, Kazuo Murahata, Yusuke Tsuka, Takeshi Itoh, Norihiko Imagawa, Tomohiro Okamoto, Yoshiharu |
| description | Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound (US) and a sonosensitizer agent. 5-Aminolevulinic acid (5-ALA) has been used as a sonodynamic sensitizer for cancer treatment. However, studies have shown that 5-ALA-based SDT has limited efficacy against malignant tumors. In this study, we examined whether artesunate (ART) could enhance the cytotoxicity of 5-ALA-based SDT against mouse mammary tumor (EMT-6) cells in vitro. In the ART, ART + US, ART + 5-ALA, and ART + 5-ALA + US groups, the cell survival rate correlated with ART concentration, and decreased with increasing concentrations of ART. Morphologically, many apoptotic and necrotic cells were observed in the ART + 5-ALA + US group. The percentage of reactive oxygen species-positive cells in the ART + 5-ALA + US group was also significantly higher than that in the 5-ALA group (p = 0.0228), and the cell death induced by ART + 5-ALA + US could be inhibited by the antioxidant N-acetylcysteine. These results show that ART offers great potential in enhancing the efficacy of 5-ALA-based SDT for the treatment of cancer. However, these results are only based on in vitro studies, and further in vivo studies are required. |
| doi_str_mv | 10.3390/molecules22040533 |
| format | Article |
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However, studies have shown that 5-ALA-based SDT has limited efficacy against malignant tumors. In this study, we examined whether artesunate (ART) could enhance the cytotoxicity of 5-ALA-based SDT against mouse mammary tumor (EMT-6) cells in vitro. In the ART, ART + US, ART + 5-ALA, and ART + 5-ALA + US groups, the cell survival rate correlated with ART concentration, and decreased with increasing concentrations of ART. Morphologically, many apoptotic and necrotic cells were observed in the ART + 5-ALA + US group. The percentage of reactive oxygen species-positive cells in the ART + 5-ALA + US group was also significantly higher than that in the 5-ALA group (p = 0.0228), and the cell death induced by ART + 5-ALA + US could be inhibited by the antioxidant N-acetylcysteine. These results show that ART offers great potential in enhancing the efficacy of 5-ALA-based SDT for the treatment of cancer. However, these results are only based on in vitro studies, and further in vivo studies are required.</description><identifier>ISSN: 1420-3049</identifier><identifier>EISSN: 1420-3049</identifier><identifier>DOI: 10.3390/molecules22040533</identifier><identifier>PMID: 28346389</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>Acetylcysteine ; Aminolevulinic acid ; Aminolevulinic Acid - pharmacology ; Animals ; Antioxidants ; Apoptosis ; Artemisinins - pharmacology ; Artesunate ; Biocompatibility ; Breast cancer ; Cancer ; Cell death ; Cell Line, Tumor ; Cell Survival - drug effects ; Cytotoxicity ; Drug Synergism ; Female ; In Vitro Techniques ; In vivo methods and tests ; Mammary gland ; Mammary Neoplasms, Animal - metabolism ; Mammary Neoplasms, Animal - therapy ; Membrane Potential, Mitochondrial - drug effects ; Mice ; Protease inhibitors ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Synergistic effect ; Tumor cells ; Tumors ; Ultrasonic Therapy - methods ; Ultrasound</subject><ispartof>Molecules (Basel, Switzerland), 2017-03, Vol.22 (4), p.533</ispartof><rights>2017. This work is licensed under https://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><rights>2017 by the authors. 2017</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c537t-b171bd8dcb0fcad08352b869baef45de103d85ec1d29bc3256ae49785059f42b3</citedby><cites>FETCH-LOGICAL-c537t-b171bd8dcb0fcad08352b869baef45de103d85ec1d29bc3256ae49785059f42b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154000/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6154000/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28346389$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Osaki, Tomohiro</creatorcontrib><creatorcontrib>Uto, Yoshihiro</creatorcontrib><creatorcontrib>Ishizuka, Masahiro</creatorcontrib><creatorcontrib>Tanaka, Tohru</creatorcontrib><creatorcontrib>Yamanaka, Nobuyasu</creatorcontrib><creatorcontrib>Kurahashi, Tsukasa</creatorcontrib><creatorcontrib>Azuma, Kazuo</creatorcontrib><creatorcontrib>Murahata, Yusuke</creatorcontrib><creatorcontrib>Tsuka, Takeshi</creatorcontrib><creatorcontrib>Itoh, Norihiko</creatorcontrib><creatorcontrib>Imagawa, Tomohiro</creatorcontrib><creatorcontrib>Okamoto, Yoshiharu</creatorcontrib><title>Artesunate Enhances the Cytotoxicity of 5-Aminolevulinic Acid-Based Sonodynamic Therapy against Mouse Mammary Tumor Cells In Vitro</title><title>Molecules (Basel, Switzerland)</title><addtitle>Molecules</addtitle><description>Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound (US) and a sonosensitizer agent. 5-Aminolevulinic acid (5-ALA) has been used as a sonodynamic sensitizer for cancer treatment. However, studies have shown that 5-ALA-based SDT has limited efficacy against malignant tumors. In this study, we examined whether artesunate (ART) could enhance the cytotoxicity of 5-ALA-based SDT against mouse mammary tumor (EMT-6) cells in vitro. In the ART, ART + US, ART + 5-ALA, and ART + 5-ALA + US groups, the cell survival rate correlated with ART concentration, and decreased with increasing concentrations of ART. Morphologically, many apoptotic and necrotic cells were observed in the ART + 5-ALA + US group. The percentage of reactive oxygen species-positive cells in the ART + 5-ALA + US group was also significantly higher than that in the 5-ALA group (p = 0.0228), and the cell death induced by ART + 5-ALA + US could be inhibited by the antioxidant N-acetylcysteine. These results show that ART offers great potential in enhancing the efficacy of 5-ALA-based SDT for the treatment of cancer. However, these results are only based on in vitro studies, and further in vivo studies are required.</description><subject>Acetylcysteine</subject><subject>Aminolevulinic acid</subject><subject>Aminolevulinic Acid - pharmacology</subject><subject>Animals</subject><subject>Antioxidants</subject><subject>Apoptosis</subject><subject>Artemisinins - pharmacology</subject><subject>Artesunate</subject><subject>Biocompatibility</subject><subject>Breast cancer</subject><subject>Cancer</subject><subject>Cell death</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Cytotoxicity</subject><subject>Drug Synergism</subject><subject>Female</subject><subject>In Vitro Techniques</subject><subject>In vivo methods and tests</subject><subject>Mammary gland</subject><subject>Mammary Neoplasms, Animal - metabolism</subject><subject>Mammary Neoplasms, Animal - therapy</subject><subject>Membrane Potential, Mitochondrial - drug effects</subject><subject>Mice</subject><subject>Protease inhibitors</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Synergistic effect</subject><subject>Tumor cells</subject><subject>Tumors</subject><subject>Ultrasonic Therapy - methods</subject><subject>Ultrasound</subject><issn>1420-3049</issn><issn>1420-3049</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</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><recordid>eNplUU1v1TAQtBCIlsIP4IIsceES8GfiXJAeTwUqteLAg6vl2Js-V4n9sJ2KXPnluGqpCpx2tTs7O6NB6CUlbznvybs5TmCXCTJjRBDJ-SN0TAUjDSeif_ygP0LPcr4ihFFB5VN0xBQXLVf9Mfq1SQXyEkwBfBr2JljIuOwBb9cSS_zprS8rjiOWzWb2oT68XiYfvMUb613zwWRw-GsM0a3BzHW820MyhxWbS-NDLvgiLhnwhZlnk1a8W-aY8BamKeOzgL_7kuJz9GQ0U4YXd_UEfft4utt-bs6_fDrbbs4bK3lXmoF2dHDK2YGM1jiiuGSDavvBwCikA0q4UxIsdawfLGeyNSD6Tkki-1GwgZ-g97e8h2WYwVkIJZlJH5K_kaaj8frvTfB7fRmvdUulIIRUgjd3BCn-WCAXPftsqxcToLrUVCnadYxyXqGv_4FexSWFak8zSpQUrRRdRdFblE0x5wTjvRhK9E3C-r-E682rhy7uL_5Eyn8Dc2Wm0w</recordid><startdate>20170327</startdate><enddate>20170327</enddate><creator>Osaki, Tomohiro</creator><creator>Uto, Yoshihiro</creator><creator>Ishizuka, Masahiro</creator><creator>Tanaka, Tohru</creator><creator>Yamanaka, Nobuyasu</creator><creator>Kurahashi, Tsukasa</creator><creator>Azuma, Kazuo</creator><creator>Murahata, Yusuke</creator><creator>Tsuka, Takeshi</creator><creator>Itoh, Norihiko</creator><creator>Imagawa, Tomohiro</creator><creator>Okamoto, Yoshiharu</creator><general>MDPI AG</general><general>MDPI</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>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20170327</creationdate><title>Artesunate Enhances the Cytotoxicity of 5-Aminolevulinic Acid-Based Sonodynamic Therapy against Mouse Mammary Tumor Cells In Vitro</title><author>Osaki, Tomohiro ; Uto, Yoshihiro ; Ishizuka, Masahiro ; Tanaka, Tohru ; Yamanaka, Nobuyasu ; Kurahashi, Tsukasa ; Azuma, Kazuo ; Murahata, Yusuke ; Tsuka, Takeshi ; Itoh, Norihiko ; Imagawa, Tomohiro ; Okamoto, Yoshiharu</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c537t-b171bd8dcb0fcad08352b869baef45de103d85ec1d29bc3256ae49785059f42b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Acetylcysteine</topic><topic>Aminolevulinic acid</topic><topic>Aminolevulinic Acid - pharmacology</topic><topic>Animals</topic><topic>Antioxidants</topic><topic>Apoptosis</topic><topic>Artemisinins - pharmacology</topic><topic>Artesunate</topic><topic>Biocompatibility</topic><topic>Breast cancer</topic><topic>Cancer</topic><topic>Cell death</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Cytotoxicity</topic><topic>Drug Synergism</topic><topic>Female</topic><topic>In Vitro Techniques</topic><topic>In vivo methods and tests</topic><topic>Mammary gland</topic><topic>Mammary Neoplasms, Animal - metabolism</topic><topic>Mammary Neoplasms, Animal - therapy</topic><topic>Membrane Potential, Mitochondrial - drug effects</topic><topic>Mice</topic><topic>Protease inhibitors</topic><topic>Reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Synergistic effect</topic><topic>Tumor cells</topic><topic>Tumors</topic><topic>Ultrasonic Therapy - methods</topic><topic>Ultrasound</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Osaki, Tomohiro</creatorcontrib><creatorcontrib>Uto, Yoshihiro</creatorcontrib><creatorcontrib>Ishizuka, Masahiro</creatorcontrib><creatorcontrib>Tanaka, Tohru</creatorcontrib><creatorcontrib>Yamanaka, Nobuyasu</creatorcontrib><creatorcontrib>Kurahashi, Tsukasa</creatorcontrib><creatorcontrib>Azuma, Kazuo</creatorcontrib><creatorcontrib>Murahata, Yusuke</creatorcontrib><creatorcontrib>Tsuka, Takeshi</creatorcontrib><creatorcontrib>Itoh, Norihiko</creatorcontrib><creatorcontrib>Imagawa, Tomohiro</creatorcontrib><creatorcontrib>Okamoto, Yoshiharu</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Molecules (Basel, Switzerland)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Osaki, Tomohiro</au><au>Uto, Yoshihiro</au><au>Ishizuka, Masahiro</au><au>Tanaka, Tohru</au><au>Yamanaka, Nobuyasu</au><au>Kurahashi, Tsukasa</au><au>Azuma, Kazuo</au><au>Murahata, Yusuke</au><au>Tsuka, Takeshi</au><au>Itoh, Norihiko</au><au>Imagawa, Tomohiro</au><au>Okamoto, Yoshiharu</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Artesunate Enhances the Cytotoxicity of 5-Aminolevulinic Acid-Based Sonodynamic Therapy against Mouse Mammary Tumor Cells In Vitro</atitle><jtitle>Molecules (Basel, Switzerland)</jtitle><addtitle>Molecules</addtitle><date>2017-03-27</date><risdate>2017</risdate><volume>22</volume><issue>4</issue><spage>533</spage><pages>533-</pages><issn>1420-3049</issn><eissn>1420-3049</eissn><abstract>Sonodynamic therapy (SDT) kills tumor cells through the synergistic effects of ultrasound (US) and a sonosensitizer agent. 5-Aminolevulinic acid (5-ALA) has been used as a sonodynamic sensitizer for cancer treatment. However, studies have shown that 5-ALA-based SDT has limited efficacy against malignant tumors. In this study, we examined whether artesunate (ART) could enhance the cytotoxicity of 5-ALA-based SDT against mouse mammary tumor (EMT-6) cells in vitro. In the ART, ART + US, ART + 5-ALA, and ART + 5-ALA + US groups, the cell survival rate correlated with ART concentration, and decreased with increasing concentrations of ART. Morphologically, many apoptotic and necrotic cells were observed in the ART + 5-ALA + US group. The percentage of reactive oxygen species-positive cells in the ART + 5-ALA + US group was also significantly higher than that in the 5-ALA group (p = 0.0228), and the cell death induced by ART + 5-ALA + US could be inhibited by the antioxidant N-acetylcysteine. These results show that ART offers great potential in enhancing the efficacy of 5-ALA-based SDT for the treatment of cancer. However, these results are only based on in vitro studies, and further in vivo studies are required.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>28346389</pmid><doi>10.3390/molecules22040533</doi><oa>free_for_read</oa></addata></record> |
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| subjects | Acetylcysteine Aminolevulinic acid Aminolevulinic Acid - pharmacology Animals Antioxidants Apoptosis Artemisinins - pharmacology Artesunate Biocompatibility Breast cancer Cancer Cell death Cell Line, Tumor Cell Survival - drug effects Cytotoxicity Drug Synergism Female In Vitro Techniques In vivo methods and tests Mammary gland Mammary Neoplasms, Animal - metabolism Mammary Neoplasms, Animal - therapy Membrane Potential, Mitochondrial - drug effects Mice Protease inhibitors Reactive oxygen species Reactive Oxygen Species - metabolism Synergistic effect Tumor cells Tumors Ultrasonic Therapy - methods Ultrasound |
| title | Artesunate Enhances the Cytotoxicity of 5-Aminolevulinic Acid-Based Sonodynamic Therapy against Mouse Mammary Tumor Cells In Vitro |
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