Simalikalactone E (SkE), a new weapon in the armamentarium of drugs targeting cancers that exhibit constitutive activation of the ERK pathway
Simalikalactone E (SkE) is a quassinoid extracted from a widely used Amazonian antimalarial remedy. Although SkE has previously been shown to have cytostatic and/or cytotoxic activities in some tumor cell lines, its mechanism of action has not yet been characterized. We show here that SkE in the hig...
Gespeichert in:
Veröffentlicht in: | Oncotarget 2012-12, Vol.3 (12), p.1688-1699 |
---|---|
Hauptverfasser: | , , , , , , , , , , , |
Format: | Artikel |
Sprache: | eng |
Schlagworte: | |
Online-Zugang: | Volltext |
Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
container_end_page | 1699 |
---|---|
container_issue | 12 |
container_start_page | 1688 |
container_title | Oncotarget |
container_volume | 3 |
creator | Robert, Guillaume Jullian, Valérie Jacquel, Arnaud Ginet, Clémence Dufies, Maeva Torino, Stephanie Pottier, Anaïs Peyrade, Frederic Tartare-Deckert, Sophie Bourdy, Geneviève Deharo, Eric Auberger, Patrick |
description | Simalikalactone E (SkE) is a quassinoid extracted from a widely used Amazonian antimalarial remedy. Although SkE has previously been shown to have cytostatic and/or cytotoxic activities in some tumor cell lines, its mechanism of action has not yet been characterized. We show here that SkE in the high nanomolar range inhibited the growth of various leukemic and solid tumor cell lines. Importantly, SkE was highly efficient at inhibiting chronic myelogenous leukemia (CML) cells that exhibit constitutive activation of the MAPK pathway and, accordingly, it impaired the phosphorylation of ERK1/2. SkE also abrogated MEK1/2 and B-Raf phosphorylation but had no effect on Ras activity. Moreover, SkE was particularly effective against melanoma cell lines carrying the B-Raf-V600E mutation. Importantly, SkE resensitized the PLX-4032-resistant 451Lu melanoma cell line (451Lu-R) and was more efficient than U0126, a MEK inhibitor, and PLX-4032 (PLX) at inducing the apoptosis of two hairy cell leukemia (HCL) patient samples carrying the B-Raf-V600E mutation. Finally, SkE was as efficient as imatinib at inhibiting tumor formation in a xenograft model of CML cells in athymic mice. In conclusion, we show that SkE, a very potent inhibitor of B-Raf-V600E, is highly effective against cancer cell lines that exhibit constitutive activation of the ERK1/2 pathway. |
doi_str_mv | 10.18632/oncotarget.791 |
format | Article |
fullrecord | <record><control><sourceid>hal_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3681504</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>oai_HAL_hal_03575413v1</sourcerecordid><originalsourceid>FETCH-LOGICAL-c427t-3059e0b4bb019ba5d9f34879baba8443a737b06abc55804b4f9d24782ea95aee3</originalsourceid><addsrcrecordid>eNpdUV1PIyEUJZs1W1N99s3wuCZbhQE6w8smxtSP2MRE12dyoUwH24GGoe32R_ifpdZVV14uuZxz7j0chI4oOaXVkBVnwZuQIE5tOi0l_Yb2qeRyUAjBvn-699Bh1z2RfAQvq0L-QL2CCVqVcriPnh9cC3M3gzmYFLzFI_zzYTY6-YUBe7vGawuL4LHzODUWQ2yhtT7PdMsWhxpP4nLa4d0Ozk-xAW9szJ0GErZ_G6ddwib4Lrm0TG6VJUwukFwWzfyt6Oj-Fi8gNWvYHKC9GuadPXyrffR4OfpzcT0Y313dXJyPB4YXZRowIqQlmmtNqNQgJrJmPPvRoKHinEHJSk2GoI0QFeGa13JSbL1bkAKsZX30e6e7WOrWTky2FGGuFjF_RtyoAE79_-Jdo6ZhpdiwooLwLHCyE2i-0K7Px2rbI0yUglO2ohl7tsOaGLou2vqdQIl6DVJ9BKlykJlx_Hm9d_y_2NgLa96fIQ</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype></control><display><type>article</type><title>Simalikalactone E (SkE), a new weapon in the armamentarium of drugs targeting cancers that exhibit constitutive activation of the ERK pathway</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Free E- Journals</source><source>PubMed Central Open Access</source><creator>Robert, Guillaume ; Jullian, Valérie ; Jacquel, Arnaud ; Ginet, Clémence ; Dufies, Maeva ; Torino, Stephanie ; Pottier, Anaïs ; Peyrade, Frederic ; Tartare-Deckert, Sophie ; Bourdy, Geneviève ; Deharo, Eric ; Auberger, Patrick</creator><creatorcontrib>Robert, Guillaume ; Jullian, Valérie ; Jacquel, Arnaud ; Ginet, Clémence ; Dufies, Maeva ; Torino, Stephanie ; Pottier, Anaïs ; Peyrade, Frederic ; Tartare-Deckert, Sophie ; Bourdy, Geneviève ; Deharo, Eric ; Auberger, Patrick</creatorcontrib><description>Simalikalactone E (SkE) is a quassinoid extracted from a widely used Amazonian antimalarial remedy. Although SkE has previously been shown to have cytostatic and/or cytotoxic activities in some tumor cell lines, its mechanism of action has not yet been characterized. We show here that SkE in the high nanomolar range inhibited the growth of various leukemic and solid tumor cell lines. Importantly, SkE was highly efficient at inhibiting chronic myelogenous leukemia (CML) cells that exhibit constitutive activation of the MAPK pathway and, accordingly, it impaired the phosphorylation of ERK1/2. SkE also abrogated MEK1/2 and B-Raf phosphorylation but had no effect on Ras activity. Moreover, SkE was particularly effective against melanoma cell lines carrying the B-Raf-V600E mutation. Importantly, SkE resensitized the PLX-4032-resistant 451Lu melanoma cell line (451Lu-R) and was more efficient than U0126, a MEK inhibitor, and PLX-4032 (PLX) at inducing the apoptosis of two hairy cell leukemia (HCL) patient samples carrying the B-Raf-V600E mutation. Finally, SkE was as efficient as imatinib at inhibiting tumor formation in a xenograft model of CML cells in athymic mice. In conclusion, we show that SkE, a very potent inhibitor of B-Raf-V600E, is highly effective against cancer cell lines that exhibit constitutive activation of the ERK1/2 pathway.</description><identifier>ISSN: 1949-2553</identifier><identifier>EISSN: 1949-2553</identifier><identifier>DOI: 10.18632/oncotarget.791</identifier><identifier>PMID: 23518796</identifier><language>eng</language><publisher>United States: Impact journals</publisher><subject>Animals ; Antineoplastic Agents - pharmacology ; Apoptosis - drug effects ; Cell Proliferation - drug effects ; Dose-Response Relationship, Drug ; Drug Resistance, Neoplasm ; Enzyme Activation ; Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors ; Extracellular Signal-Regulated MAP Kinases - metabolism ; Female ; HEK293 Cells ; Humans ; K562 Cells ; Leukemia, Hairy Cell - enzymology ; Leukemia, Hairy Cell - genetics ; Leukemia, Hairy Cell - pathology ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - enzymology ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics ; Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology ; Life Sciences ; MAP Kinase Kinase Kinases - antagonists & inhibitors ; MAP Kinase Kinase Kinases - metabolism ; Melanoma - enzymology ; Melanoma - genetics ; Melanoma - pathology ; Mice ; Mice, Nude ; Molecular Targeted Therapy ; Mutation ; Phosphorylation ; Protein Kinase Inhibitors - pharmacology ; Proto-Oncogene Proteins B-raf - antagonists & inhibitors ; Proto-Oncogene Proteins B-raf - genetics ; Proto-Oncogene Proteins B-raf - metabolism ; Quassins - pharmacology ; Research Papers ; Signal Transduction - drug effects ; Skin Neoplasms - enzymology ; Skin Neoplasms - genetics ; Skin Neoplasms - pathology ; Time Factors ; Transfection ; Tumor Burden - drug effects ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays</subject><ispartof>Oncotarget, 2012-12, Vol.3 (12), p.1688-1699</ispartof><rights>Attribution</rights><rights>Copyright: © 2012 Robert et al. 2012</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c427t-3059e0b4bb019ba5d9f34879baba8443a737b06abc55804b4f9d24782ea95aee3</citedby><cites>FETCH-LOGICAL-c427t-3059e0b4bb019ba5d9f34879baba8443a737b06abc55804b4f9d24782ea95aee3</cites><orcidid>0000-0002-2481-8275 ; 0000-0001-5062-8048 ; 0000-0003-1732-0388 ; 0000-0002-5664-9517</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/PMC3681504/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3681504/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23518796$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://ut3-toulouseinp.hal.science/hal-03575413$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Robert, Guillaume</creatorcontrib><creatorcontrib>Jullian, Valérie</creatorcontrib><creatorcontrib>Jacquel, Arnaud</creatorcontrib><creatorcontrib>Ginet, Clémence</creatorcontrib><creatorcontrib>Dufies, Maeva</creatorcontrib><creatorcontrib>Torino, Stephanie</creatorcontrib><creatorcontrib>Pottier, Anaïs</creatorcontrib><creatorcontrib>Peyrade, Frederic</creatorcontrib><creatorcontrib>Tartare-Deckert, Sophie</creatorcontrib><creatorcontrib>Bourdy, Geneviève</creatorcontrib><creatorcontrib>Deharo, Eric</creatorcontrib><creatorcontrib>Auberger, Patrick</creatorcontrib><title>Simalikalactone E (SkE), a new weapon in the armamentarium of drugs targeting cancers that exhibit constitutive activation of the ERK pathway</title><title>Oncotarget</title><addtitle>Oncotarget</addtitle><description>Simalikalactone E (SkE) is a quassinoid extracted from a widely used Amazonian antimalarial remedy. Although SkE has previously been shown to have cytostatic and/or cytotoxic activities in some tumor cell lines, its mechanism of action has not yet been characterized. We show here that SkE in the high nanomolar range inhibited the growth of various leukemic and solid tumor cell lines. Importantly, SkE was highly efficient at inhibiting chronic myelogenous leukemia (CML) cells that exhibit constitutive activation of the MAPK pathway and, accordingly, it impaired the phosphorylation of ERK1/2. SkE also abrogated MEK1/2 and B-Raf phosphorylation but had no effect on Ras activity. Moreover, SkE was particularly effective against melanoma cell lines carrying the B-Raf-V600E mutation. Importantly, SkE resensitized the PLX-4032-resistant 451Lu melanoma cell line (451Lu-R) and was more efficient than U0126, a MEK inhibitor, and PLX-4032 (PLX) at inducing the apoptosis of two hairy cell leukemia (HCL) patient samples carrying the B-Raf-V600E mutation. Finally, SkE was as efficient as imatinib at inhibiting tumor formation in a xenograft model of CML cells in athymic mice. In conclusion, we show that SkE, a very potent inhibitor of B-Raf-V600E, is highly effective against cancer cell lines that exhibit constitutive activation of the ERK1/2 pathway.</description><subject>Animals</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Resistance, Neoplasm</subject><subject>Enzyme Activation</subject><subject>Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors</subject><subject>Extracellular Signal-Regulated MAP Kinases - metabolism</subject><subject>Female</subject><subject>HEK293 Cells</subject><subject>Humans</subject><subject>K562 Cells</subject><subject>Leukemia, Hairy Cell - enzymology</subject><subject>Leukemia, Hairy Cell - genetics</subject><subject>Leukemia, Hairy Cell - pathology</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - enzymology</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics</subject><subject>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology</subject><subject>Life Sciences</subject><subject>MAP Kinase Kinase Kinases - antagonists & inhibitors</subject><subject>MAP Kinase Kinase Kinases - metabolism</subject><subject>Melanoma - enzymology</subject><subject>Melanoma - genetics</subject><subject>Melanoma - pathology</subject><subject>Mice</subject><subject>Mice, Nude</subject><subject>Molecular Targeted Therapy</subject><subject>Mutation</subject><subject>Phosphorylation</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Proto-Oncogene Proteins B-raf - antagonists & inhibitors</subject><subject>Proto-Oncogene Proteins B-raf - genetics</subject><subject>Proto-Oncogene Proteins B-raf - metabolism</subject><subject>Quassins - pharmacology</subject><subject>Research Papers</subject><subject>Signal Transduction - drug effects</subject><subject>Skin Neoplasms - enzymology</subject><subject>Skin Neoplasms - genetics</subject><subject>Skin Neoplasms - pathology</subject><subject>Time Factors</subject><subject>Transfection</subject><subject>Tumor Burden - drug effects</subject><subject>Tumor Cells, Cultured</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1949-2553</issn><issn>1949-2553</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdUV1PIyEUJZs1W1N99s3wuCZbhQE6w8smxtSP2MRE12dyoUwH24GGoe32R_ifpdZVV14uuZxz7j0chI4oOaXVkBVnwZuQIE5tOi0l_Yb2qeRyUAjBvn-699Bh1z2RfAQvq0L-QL2CCVqVcriPnh9cC3M3gzmYFLzFI_zzYTY6-YUBe7vGawuL4LHzODUWQ2yhtT7PdMsWhxpP4nLa4d0Ozk-xAW9szJ0GErZ_G6ddwib4Lrm0TG6VJUwukFwWzfyt6Oj-Fi8gNWvYHKC9GuadPXyrffR4OfpzcT0Y313dXJyPB4YXZRowIqQlmmtNqNQgJrJmPPvRoKHinEHJSk2GoI0QFeGa13JSbL1bkAKsZX30e6e7WOrWTky2FGGuFjF_RtyoAE79_-Jdo6ZhpdiwooLwLHCyE2i-0K7Px2rbI0yUglO2ohl7tsOaGLou2vqdQIl6DVJ9BKlykJlx_Hm9d_y_2NgLa96fIQ</recordid><startdate>20121201</startdate><enddate>20121201</enddate><creator>Robert, Guillaume</creator><creator>Jullian, Valérie</creator><creator>Jacquel, Arnaud</creator><creator>Ginet, Clémence</creator><creator>Dufies, Maeva</creator><creator>Torino, Stephanie</creator><creator>Pottier, Anaïs</creator><creator>Peyrade, Frederic</creator><creator>Tartare-Deckert, Sophie</creator><creator>Bourdy, Geneviève</creator><creator>Deharo, Eric</creator><creator>Auberger, Patrick</creator><general>Impact journals</general><general>Impact Journals LLC</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>1XC</scope><scope>VOOES</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-2481-8275</orcidid><orcidid>https://orcid.org/0000-0001-5062-8048</orcidid><orcidid>https://orcid.org/0000-0003-1732-0388</orcidid><orcidid>https://orcid.org/0000-0002-5664-9517</orcidid></search><sort><creationdate>20121201</creationdate><title>Simalikalactone E (SkE), a new weapon in the armamentarium of drugs targeting cancers that exhibit constitutive activation of the ERK pathway</title><author>Robert, Guillaume ; Jullian, Valérie ; Jacquel, Arnaud ; Ginet, Clémence ; Dufies, Maeva ; Torino, Stephanie ; Pottier, Anaïs ; Peyrade, Frederic ; Tartare-Deckert, Sophie ; Bourdy, Geneviève ; Deharo, Eric ; Auberger, Patrick</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c427t-3059e0b4bb019ba5d9f34879baba8443a737b06abc55804b4f9d24782ea95aee3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Animals</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Resistance, Neoplasm</topic><topic>Enzyme Activation</topic><topic>Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors</topic><topic>Extracellular Signal-Regulated MAP Kinases - metabolism</topic><topic>Female</topic><topic>HEK293 Cells</topic><topic>Humans</topic><topic>K562 Cells</topic><topic>Leukemia, Hairy Cell - enzymology</topic><topic>Leukemia, Hairy Cell - genetics</topic><topic>Leukemia, Hairy Cell - pathology</topic><topic>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy</topic><topic>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - enzymology</topic><topic>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics</topic><topic>Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology</topic><topic>Life Sciences</topic><topic>MAP Kinase Kinase Kinases - antagonists & inhibitors</topic><topic>MAP Kinase Kinase Kinases - metabolism</topic><topic>Melanoma - enzymology</topic><topic>Melanoma - genetics</topic><topic>Melanoma - pathology</topic><topic>Mice</topic><topic>Mice, Nude</topic><topic>Molecular Targeted Therapy</topic><topic>Mutation</topic><topic>Phosphorylation</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Proto-Oncogene Proteins B-raf - antagonists & inhibitors</topic><topic>Proto-Oncogene Proteins B-raf - genetics</topic><topic>Proto-Oncogene Proteins B-raf - metabolism</topic><topic>Quassins - pharmacology</topic><topic>Research Papers</topic><topic>Signal Transduction - drug effects</topic><topic>Skin Neoplasms - enzymology</topic><topic>Skin Neoplasms - genetics</topic><topic>Skin Neoplasms - pathology</topic><topic>Time Factors</topic><topic>Transfection</topic><topic>Tumor Burden - drug effects</topic><topic>Tumor Cells, Cultured</topic><topic>Xenograft Model Antitumor Assays</topic><toplevel>online_resources</toplevel><creatorcontrib>Robert, Guillaume</creatorcontrib><creatorcontrib>Jullian, Valérie</creatorcontrib><creatorcontrib>Jacquel, Arnaud</creatorcontrib><creatorcontrib>Ginet, Clémence</creatorcontrib><creatorcontrib>Dufies, Maeva</creatorcontrib><creatorcontrib>Torino, Stephanie</creatorcontrib><creatorcontrib>Pottier, Anaïs</creatorcontrib><creatorcontrib>Peyrade, Frederic</creatorcontrib><creatorcontrib>Tartare-Deckert, Sophie</creatorcontrib><creatorcontrib>Bourdy, Geneviève</creatorcontrib><creatorcontrib>Deharo, Eric</creatorcontrib><creatorcontrib>Auberger, Patrick</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Oncotarget</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Robert, Guillaume</au><au>Jullian, Valérie</au><au>Jacquel, Arnaud</au><au>Ginet, Clémence</au><au>Dufies, Maeva</au><au>Torino, Stephanie</au><au>Pottier, Anaïs</au><au>Peyrade, Frederic</au><au>Tartare-Deckert, Sophie</au><au>Bourdy, Geneviève</au><au>Deharo, Eric</au><au>Auberger, Patrick</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Simalikalactone E (SkE), a new weapon in the armamentarium of drugs targeting cancers that exhibit constitutive activation of the ERK pathway</atitle><jtitle>Oncotarget</jtitle><addtitle>Oncotarget</addtitle><date>2012-12-01</date><risdate>2012</risdate><volume>3</volume><issue>12</issue><spage>1688</spage><epage>1699</epage><pages>1688-1699</pages><issn>1949-2553</issn><eissn>1949-2553</eissn><abstract>Simalikalactone E (SkE) is a quassinoid extracted from a widely used Amazonian antimalarial remedy. Although SkE has previously been shown to have cytostatic and/or cytotoxic activities in some tumor cell lines, its mechanism of action has not yet been characterized. We show here that SkE in the high nanomolar range inhibited the growth of various leukemic and solid tumor cell lines. Importantly, SkE was highly efficient at inhibiting chronic myelogenous leukemia (CML) cells that exhibit constitutive activation of the MAPK pathway and, accordingly, it impaired the phosphorylation of ERK1/2. SkE also abrogated MEK1/2 and B-Raf phosphorylation but had no effect on Ras activity. Moreover, SkE was particularly effective against melanoma cell lines carrying the B-Raf-V600E mutation. Importantly, SkE resensitized the PLX-4032-resistant 451Lu melanoma cell line (451Lu-R) and was more efficient than U0126, a MEK inhibitor, and PLX-4032 (PLX) at inducing the apoptosis of two hairy cell leukemia (HCL) patient samples carrying the B-Raf-V600E mutation. Finally, SkE was as efficient as imatinib at inhibiting tumor formation in a xenograft model of CML cells in athymic mice. In conclusion, we show that SkE, a very potent inhibitor of B-Raf-V600E, is highly effective against cancer cell lines that exhibit constitutive activation of the ERK1/2 pathway.</abstract><cop>United States</cop><pub>Impact journals</pub><pmid>23518796</pmid><doi>10.18632/oncotarget.791</doi><tpages>12</tpages><orcidid>https://orcid.org/0000-0002-2481-8275</orcidid><orcidid>https://orcid.org/0000-0001-5062-8048</orcidid><orcidid>https://orcid.org/0000-0003-1732-0388</orcidid><orcidid>https://orcid.org/0000-0002-5664-9517</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1949-2553 |
ispartof | Oncotarget, 2012-12, Vol.3 (12), p.1688-1699 |
issn | 1949-2553 1949-2553 |
language | eng |
recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_3681504 |
source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Free E- Journals; PubMed Central Open Access |
subjects | Animals Antineoplastic Agents - pharmacology Apoptosis - drug effects Cell Proliferation - drug effects Dose-Response Relationship, Drug Drug Resistance, Neoplasm Enzyme Activation Extracellular Signal-Regulated MAP Kinases - antagonists & inhibitors Extracellular Signal-Regulated MAP Kinases - metabolism Female HEK293 Cells Humans K562 Cells Leukemia, Hairy Cell - enzymology Leukemia, Hairy Cell - genetics Leukemia, Hairy Cell - pathology Leukemia, Myelogenous, Chronic, BCR-ABL Positive - drug therapy Leukemia, Myelogenous, Chronic, BCR-ABL Positive - enzymology Leukemia, Myelogenous, Chronic, BCR-ABL Positive - genetics Leukemia, Myelogenous, Chronic, BCR-ABL Positive - pathology Life Sciences MAP Kinase Kinase Kinases - antagonists & inhibitors MAP Kinase Kinase Kinases - metabolism Melanoma - enzymology Melanoma - genetics Melanoma - pathology Mice Mice, Nude Molecular Targeted Therapy Mutation Phosphorylation Protein Kinase Inhibitors - pharmacology Proto-Oncogene Proteins B-raf - antagonists & inhibitors Proto-Oncogene Proteins B-raf - genetics Proto-Oncogene Proteins B-raf - metabolism Quassins - pharmacology Research Papers Signal Transduction - drug effects Skin Neoplasms - enzymology Skin Neoplasms - genetics Skin Neoplasms - pathology Time Factors Transfection Tumor Burden - drug effects Tumor Cells, Cultured Xenograft Model Antitumor Assays |
title | Simalikalactone E (SkE), a new weapon in the armamentarium of drugs targeting cancers that exhibit constitutive activation of the ERK pathway |
url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-20T04%3A43%3A04IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-hal_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Simalikalactone%20E%20(SkE),%20a%20new%20weapon%20in%20the%20armamentarium%20of%20drugs%20targeting%20cancers%20that%20exhibit%20constitutive%20activation%20of%20the%20ERK%20pathway&rft.jtitle=Oncotarget&rft.au=Robert,%20Guillaume&rft.date=2012-12-01&rft.volume=3&rft.issue=12&rft.spage=1688&rft.epage=1699&rft.pages=1688-1699&rft.issn=1949-2553&rft.eissn=1949-2553&rft_id=info:doi/10.18632/oncotarget.791&rft_dat=%3Chal_pubme%3Eoai_HAL_hal_03575413v1%3C/hal_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/23518796&rfr_iscdi=true |