In vitro evaluation of the cytotoxic and genotoxic effects of artemether, an antimalarial drug, in a gastric cancer cell line (PG100)
ABSTRACT Artemisinin is a sesquiterpene lactone endoperoxide, obtained from Artemisia annua, and extensively used as an antimalarial drug. Many studies have reported the genotoxic and cytotoxic effects of artemisinins; however, there are no studies that compare such effects between cancer cell lines...
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| Veröffentlicht in: | Journal of applied toxicology 2013-02, Vol.33 (2), p.151-156 |
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| creator | Alcântara, Diego Di Felipe Ávila Ribeiro, Helem Ferreira Cardoso, Plínio Cerqueira dos Santos Araújo, Taíssa Maíra Thomaz Burbano, Rommel Rodriguez Guimarães, Adriana Costa Khayat, André Salim de Oliveira Bahia, Marcelo |
| description | ABSTRACT
Artemisinin is a sesquiterpene lactone endoperoxide, obtained from Artemisia annua, and extensively used as an antimalarial drug. Many studies have reported the genotoxic and cytotoxic effects of artemisinins; however, there are no studies that compare such effects between cancer cell lines and normal human cells after treatment with artemether, an artemisinin derivative. Gastric cancer is the fourth most frequent type of cancer and the second highest cause of cancer mortality worldwide. Thus, the aim of this study was to evaluate the in vitro genotoxic and cytotoxic effects induced by artemether in gastric cancer cell line (PG100) and compare them with the results obtained in human lymphocytes exposed to the same conditions. We used MTT (3‐(4,5‐methylthiazol‐2‐yl)‐2, 5‐diphenyl‐tetrazolium bromide) assay, comet assay and ethidium bromide/acridine orange viability staining to evaluate the cytotoxic and genotoxic effects of artemether in PG100. MTT assay showed a decrease in the survival percentages for both cell types treated with different concentrations of artemether (P |
| doi_str_mv | 10.1002/jat.1734 |
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Artemisinin is a sesquiterpene lactone endoperoxide, obtained from Artemisia annua, and extensively used as an antimalarial drug. Many studies have reported the genotoxic and cytotoxic effects of artemisinins; however, there are no studies that compare such effects between cancer cell lines and normal human cells after treatment with artemether, an artemisinin derivative. Gastric cancer is the fourth most frequent type of cancer and the second highest cause of cancer mortality worldwide. Thus, the aim of this study was to evaluate the in vitro genotoxic and cytotoxic effects induced by artemether in gastric cancer cell line (PG100) and compare them with the results obtained in human lymphocytes exposed to the same conditions. We used MTT (3‐(4,5‐methylthiazol‐2‐yl)‐2, 5‐diphenyl‐tetrazolium bromide) assay, comet assay and ethidium bromide/acridine orange viability staining to evaluate the cytotoxic and genotoxic effects of artemether in PG100. MTT assay showed a decrease in the survival percentages for both cell types treated with different concentrations of artemether (P < 0.05). PG100 also showed a significant dose‐dependent increase in DNA damage index at concentrations of 119.4 and 238.8 µg ml−1 (P < 0.05). Our results showed that artemether induced necrosis in PG100 at concentrations of 238.8 and 477.6 µg ml−1, for all the tested harvest times (P < 0.05). In lymphocytes, artemether induced both apoptosis and necrosis at concentrations of 238.8 and 477.6 µg ml−1, for all the tested harvest times (P < 0.05). In conclusion, human lymphocytes were more sensitive to the cytotoxic effects of the antimalarial drug than the gastric cancer cell line PG100. Copyright © 2011 John Wiley & Sons, Ltd.
We conducted a cytotoxic and genotoxic study in PG100 cell line and human lymphocytes after treatment with artemether. Using MTT assay, comet assay and ethidium bromide/acridine orange viability staining, we showed that artemether has a cytotoxic effect and induces necrosis in the PG100 gastric cancer cell line. However, its use as a possible antineoplastic drug is not recommended, since the cytotoxic effects were more consistent in human lymphocytes.</description><identifier>ISSN: 0260-437X</identifier><identifier>EISSN: 1099-1263</identifier><identifier>DOI: 10.1002/jat.1734</identifier><identifier>PMID: 21953315</identifier><language>eng</language><publisher>Chichester, UK: John Wiley & Sons, Ltd</publisher><subject>Antimalarials - pharmacology ; Antimalarials - toxicity ; Antineoplastic Agents - pharmacology ; Antineoplastic Agents - toxicity ; apoptosis ; Apoptosis - drug effects ; artemether ; Artemisinins - pharmacology ; Artemisinins - toxicity ; Assaying ; Biotechnology ; Bromides ; Cancer ; Cell Line, Tumor ; Cell Survival - drug effects ; Comet Assay ; Cytotoxicity ; DNA Damage ; Dose-Response Relationship, Drug ; Drugs ; Gastric cancer ; Genotoxicity ; Human ; Humans ; Lymphocytes ; Lymphocytes - drug effects ; Lymphocytes - pathology ; Malaria ; Microscopy, Fluorescence ; MTT assay ; Mutagens - pharmacology ; Mutagens - toxicity ; Necrosis ; Pharmacology</subject><ispartof>Journal of applied toxicology, 2013-02, Vol.33 (2), p.151-156</ispartof><rights>Copyright © 2011 John Wiley & Sons, Ltd.</rights><rights>Copyright © 2012 John Wiley & Sons, Ltd.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4864-914b854b76c213a9341a1c565202f2f37b3e73948892a519986f9aa6998b30503</citedby><cites>FETCH-LOGICAL-c4864-914b854b76c213a9341a1c565202f2f37b3e73948892a519986f9aa6998b30503</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjat.1734$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjat.1734$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,776,780,1411,27903,27904,45553,45554</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21953315$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Alcântara, Diego Di Felipe Ávila</creatorcontrib><creatorcontrib>Ribeiro, Helem Ferreira</creatorcontrib><creatorcontrib>Cardoso, Plínio Cerqueira dos Santos</creatorcontrib><creatorcontrib>Araújo, Taíssa Maíra Thomaz</creatorcontrib><creatorcontrib>Burbano, Rommel Rodriguez</creatorcontrib><creatorcontrib>Guimarães, Adriana Costa</creatorcontrib><creatorcontrib>Khayat, André Salim</creatorcontrib><creatorcontrib>de Oliveira Bahia, Marcelo</creatorcontrib><title>In vitro evaluation of the cytotoxic and genotoxic effects of artemether, an antimalarial drug, in a gastric cancer cell line (PG100)</title><title>Journal of applied toxicology</title><addtitle>J. Appl. Toxicol</addtitle><description>ABSTRACT
Artemisinin is a sesquiterpene lactone endoperoxide, obtained from Artemisia annua, and extensively used as an antimalarial drug. Many studies have reported the genotoxic and cytotoxic effects of artemisinins; however, there are no studies that compare such effects between cancer cell lines and normal human cells after treatment with artemether, an artemisinin derivative. Gastric cancer is the fourth most frequent type of cancer and the second highest cause of cancer mortality worldwide. Thus, the aim of this study was to evaluate the in vitro genotoxic and cytotoxic effects induced by artemether in gastric cancer cell line (PG100) and compare them with the results obtained in human lymphocytes exposed to the same conditions. We used MTT (3‐(4,5‐methylthiazol‐2‐yl)‐2, 5‐diphenyl‐tetrazolium bromide) assay, comet assay and ethidium bromide/acridine orange viability staining to evaluate the cytotoxic and genotoxic effects of artemether in PG100. MTT assay showed a decrease in the survival percentages for both cell types treated with different concentrations of artemether (P < 0.05). PG100 also showed a significant dose‐dependent increase in DNA damage index at concentrations of 119.4 and 238.8 µg ml−1 (P < 0.05). Our results showed that artemether induced necrosis in PG100 at concentrations of 238.8 and 477.6 µg ml−1, for all the tested harvest times (P < 0.05). In lymphocytes, artemether induced both apoptosis and necrosis at concentrations of 238.8 and 477.6 µg ml−1, for all the tested harvest times (P < 0.05). In conclusion, human lymphocytes were more sensitive to the cytotoxic effects of the antimalarial drug than the gastric cancer cell line PG100. Copyright © 2011 John Wiley & Sons, Ltd.
We conducted a cytotoxic and genotoxic study in PG100 cell line and human lymphocytes after treatment with artemether. Using MTT assay, comet assay and ethidium bromide/acridine orange viability staining, we showed that artemether has a cytotoxic effect and induces necrosis in the PG100 gastric cancer cell line. However, its use as a possible antineoplastic drug is not recommended, since the cytotoxic effects were more consistent in human lymphocytes.</description><subject>Antimalarials - pharmacology</subject><subject>Antimalarials - toxicity</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antineoplastic Agents - toxicity</subject><subject>apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>artemether</subject><subject>Artemisinins - pharmacology</subject><subject>Artemisinins - toxicity</subject><subject>Assaying</subject><subject>Biotechnology</subject><subject>Bromides</subject><subject>Cancer</subject><subject>Cell Line, Tumor</subject><subject>Cell Survival - drug effects</subject><subject>Comet Assay</subject><subject>Cytotoxicity</subject><subject>DNA Damage</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drugs</subject><subject>Gastric cancer</subject><subject>Genotoxicity</subject><subject>Human</subject><subject>Humans</subject><subject>Lymphocytes</subject><subject>Lymphocytes - drug effects</subject><subject>Lymphocytes - pathology</subject><subject>Malaria</subject><subject>Microscopy, Fluorescence</subject><subject>MTT assay</subject><subject>Mutagens - pharmacology</subject><subject>Mutagens - toxicity</subject><subject>Necrosis</subject><subject>Pharmacology</subject><issn>0260-437X</issn><issn>1099-1263</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkV1rFDEUhoNY7NoK_gIJeFOh0-ZrJpPLtuq2UlSk0t6FTPbMmnV2UpNM7f4A_3cz7FhEECGQrycP5-RF6CUlR5QQdrwy6YhKLp6gGSVKFZRV_CmaEVaRQnB5s4uex7giJN-x-hnaZVSVnNNyhn5d9PjOpeAx3JluMMn5HvsWp2-A7Sb55O-dxaZf4CX00w7aFmyKI2ZCgjVkOBxmKI_k1qYzwZkOL8KwPMQun-KliSnkl9b0FgK20HW4cz3gg8_z3MCbfbTTmi7Ci2neQ1_fv7s6Oy8uP80vzk4uCyvqShSKiqYuRSMryyg3igtqqC2rkhHWspbLhoPkStS1YqakStVVq4yp8qLhpCR8Dx1svbfB_xggJr12cazG9OCHqKngijEiaf1_lElOGduir_9CV34IfW5kFOZqavWn0AYfY4BW34b8WWGjKdFjijqnqMcUM_pqEg7NGhaP4O_YMlBsgZ-ug80_RfrDydUknHgXE9w_8iZ815XkstTXH-f6-vQtlfLLjT7nD2Desek</recordid><startdate>201302</startdate><enddate>201302</enddate><creator>Alcântara, Diego Di Felipe Ávila</creator><creator>Ribeiro, Helem Ferreira</creator><creator>Cardoso, Plínio Cerqueira dos Santos</creator><creator>Araújo, Taíssa Maíra Thomaz</creator><creator>Burbano, Rommel Rodriguez</creator><creator>Guimarães, Adriana Costa</creator><creator>Khayat, André Salim</creator><creator>de Oliveira Bahia, Marcelo</creator><general>John Wiley & Sons, Ltd</general><general>Wiley Subscription Services, Inc</general><scope>BSCLL</scope><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>7ST</scope><scope>7TK</scope><scope>7U7</scope><scope>C1K</scope><scope>K9.</scope><scope>SOI</scope><scope>7X8</scope><scope>8FD</scope><scope>FR3</scope><scope>KR7</scope></search><sort><creationdate>201302</creationdate><title>In vitro evaluation of the cytotoxic and genotoxic effects of artemether, an antimalarial drug, in a gastric cancer cell line (PG100)</title><author>Alcântara, Diego Di Felipe Ávila ; Ribeiro, Helem Ferreira ; Cardoso, Plínio Cerqueira dos Santos ; Araújo, Taíssa Maíra Thomaz ; Burbano, Rommel Rodriguez ; Guimarães, Adriana Costa ; Khayat, André Salim ; de Oliveira Bahia, Marcelo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4864-914b854b76c213a9341a1c565202f2f37b3e73948892a519986f9aa6998b30503</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2013</creationdate><topic>Antimalarials - pharmacology</topic><topic>Antimalarials - toxicity</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antineoplastic Agents - toxicity</topic><topic>apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>artemether</topic><topic>Artemisinins - pharmacology</topic><topic>Artemisinins - toxicity</topic><topic>Assaying</topic><topic>Biotechnology</topic><topic>Bromides</topic><topic>Cancer</topic><topic>Cell Line, Tumor</topic><topic>Cell Survival - drug effects</topic><topic>Comet Assay</topic><topic>Cytotoxicity</topic><topic>DNA Damage</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drugs</topic><topic>Gastric cancer</topic><topic>Genotoxicity</topic><topic>Human</topic><topic>Humans</topic><topic>Lymphocytes</topic><topic>Lymphocytes - drug effects</topic><topic>Lymphocytes - pathology</topic><topic>Malaria</topic><topic>Microscopy, Fluorescence</topic><topic>MTT assay</topic><topic>Mutagens - pharmacology</topic><topic>Mutagens - toxicity</topic><topic>Necrosis</topic><topic>Pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alcântara, Diego Di Felipe Ávila</creatorcontrib><creatorcontrib>Ribeiro, Helem Ferreira</creatorcontrib><creatorcontrib>Cardoso, Plínio Cerqueira dos Santos</creatorcontrib><creatorcontrib>Araújo, Taíssa Maíra Thomaz</creatorcontrib><creatorcontrib>Burbano, Rommel Rodriguez</creatorcontrib><creatorcontrib>Guimarães, Adriana Costa</creatorcontrib><creatorcontrib>Khayat, André Salim</creatorcontrib><creatorcontrib>de Oliveira Bahia, Marcelo</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Environment Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Environment Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Civil Engineering Abstracts</collection><jtitle>Journal of applied toxicology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alcântara, Diego Di Felipe Ávila</au><au>Ribeiro, Helem Ferreira</au><au>Cardoso, Plínio Cerqueira dos Santos</au><au>Araújo, Taíssa Maíra Thomaz</au><au>Burbano, Rommel Rodriguez</au><au>Guimarães, Adriana Costa</au><au>Khayat, André Salim</au><au>de Oliveira Bahia, Marcelo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>In vitro evaluation of the cytotoxic and genotoxic effects of artemether, an antimalarial drug, in a gastric cancer cell line (PG100)</atitle><jtitle>Journal of applied toxicology</jtitle><addtitle>J. Appl. Toxicol</addtitle><date>2013-02</date><risdate>2013</risdate><volume>33</volume><issue>2</issue><spage>151</spage><epage>156</epage><pages>151-156</pages><issn>0260-437X</issn><eissn>1099-1263</eissn><abstract>ABSTRACT
Artemisinin is a sesquiterpene lactone endoperoxide, obtained from Artemisia annua, and extensively used as an antimalarial drug. Many studies have reported the genotoxic and cytotoxic effects of artemisinins; however, there are no studies that compare such effects between cancer cell lines and normal human cells after treatment with artemether, an artemisinin derivative. Gastric cancer is the fourth most frequent type of cancer and the second highest cause of cancer mortality worldwide. Thus, the aim of this study was to evaluate the in vitro genotoxic and cytotoxic effects induced by artemether in gastric cancer cell line (PG100) and compare them with the results obtained in human lymphocytes exposed to the same conditions. We used MTT (3‐(4,5‐methylthiazol‐2‐yl)‐2, 5‐diphenyl‐tetrazolium bromide) assay, comet assay and ethidium bromide/acridine orange viability staining to evaluate the cytotoxic and genotoxic effects of artemether in PG100. MTT assay showed a decrease in the survival percentages for both cell types treated with different concentrations of artemether (P < 0.05). PG100 also showed a significant dose‐dependent increase in DNA damage index at concentrations of 119.4 and 238.8 µg ml−1 (P < 0.05). Our results showed that artemether induced necrosis in PG100 at concentrations of 238.8 and 477.6 µg ml−1, for all the tested harvest times (P < 0.05). In lymphocytes, artemether induced both apoptosis and necrosis at concentrations of 238.8 and 477.6 µg ml−1, for all the tested harvest times (P < 0.05). In conclusion, human lymphocytes were more sensitive to the cytotoxic effects of the antimalarial drug than the gastric cancer cell line PG100. Copyright © 2011 John Wiley & Sons, Ltd.
We conducted a cytotoxic and genotoxic study in PG100 cell line and human lymphocytes after treatment with artemether. Using MTT assay, comet assay and ethidium bromide/acridine orange viability staining, we showed that artemether has a cytotoxic effect and induces necrosis in the PG100 gastric cancer cell line. However, its use as a possible antineoplastic drug is not recommended, since the cytotoxic effects were more consistent in human lymphocytes.</abstract><cop>Chichester, UK</cop><pub>John Wiley & Sons, Ltd</pub><pmid>21953315</pmid><doi>10.1002/jat.1734</doi><tpages>6</tpages></addata></record> |
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| subjects | Antimalarials - pharmacology Antimalarials - toxicity Antineoplastic Agents - pharmacology Antineoplastic Agents - toxicity apoptosis Apoptosis - drug effects artemether Artemisinins - pharmacology Artemisinins - toxicity Assaying Biotechnology Bromides Cancer Cell Line, Tumor Cell Survival - drug effects Comet Assay Cytotoxicity DNA Damage Dose-Response Relationship, Drug Drugs Gastric cancer Genotoxicity Human Humans Lymphocytes Lymphocytes - drug effects Lymphocytes - pathology Malaria Microscopy, Fluorescence MTT assay Mutagens - pharmacology Mutagens - toxicity Necrosis Pharmacology |
| title | In vitro evaluation of the cytotoxic and genotoxic effects of artemether, an antimalarial drug, in a gastric cancer cell line (PG100) |
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