Onconase Restores Cytotoxicity in Dabrafenib-Resistant A375 Human Melanoma Cells and Affects Cell Migration, Invasion and Colony Formation Capability
Melanoma is a lethal tumor because of its severe metastatic potential, and serine/threonine-protein kinase B-raf inhibitors (BRAFi) are used in patients harboring BRAF-mutation. Unfortunately, BRAFi induce resistance. Therefore, we tested the activity of onconase (ONC), a cytotoxic RNase variant, ag...
Gespeichert in:
| Veröffentlicht in: | International journal of molecular sciences 2019-11, Vol.20 (23), p.5980 |
|---|---|
| Hauptverfasser: | , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | |
|---|---|
| container_issue | 23 |
| container_start_page | 5980 |
| container_title | International journal of molecular sciences |
| container_volume | 20 |
| creator | Raineri, Alice Fasoli, Sabrina Campagnari, Rachele Gotte, Giovanni Menegazzi, Marta |
| description | Melanoma is a lethal tumor because of its severe metastatic potential, and serine/threonine-protein kinase B-raf inhibitors (BRAFi) are used in patients harboring BRAF-mutation. Unfortunately, BRAFi induce resistance. Therefore, we tested the activity of onconase (ONC), a cytotoxic RNase variant, against BRAFi-resistant cells to re-establish the efficacy of the chemotherapy. To do so, an A375 dabrafenib-resistant (A375DR) melanoma cell subpopulation was selected and its behavior compared with that of parental (A375P) cells by crystal violet, 5-Bromo-2'-deoxyuridine incorporation, and cleaved poly(ADP-ribose) polymerase 1 (PARP1) western blot measurements. Then, nuclear p65 Nuclear Factor kappaB (NF-κB) and IκB kinases-α/β (IKK) phosphorylation levels were measured. Gelatin zymography was performed to evaluate metalloproteinase 2 (MMP2) activity. In addition, assays to measure migration, invasion and soft agar colony formation were performed to examine the tumor cell dissemination propensity. ONC affected the total viability and the proliferation rate of both A375P and A375DR cell subpopulations in a dose-dependent manner and also induced apoptotic cell death. Among its pleiotropic effects, ONC reduced nuclear p65 NF-κB amount and IKK phosphorylation level, as well as MMP2 activity in both cell subpopulations. ONC decreased cell colony formation, migration, and invasion capability. Notably, it induced apoptosis and inhibited colony formation and invasiveness more extensively in A375DR than in A375P cells. In conclusion, ONC successfully counteracts melanoma malignancy especially in BRAFi-resistant cells and could become a tool against melanoma recurrence. |
| doi_str_mv | 10.3390/ijms20235980 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6928899</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>2548650515</sourcerecordid><originalsourceid>FETCH-LOGICAL-c478t-26f88a877a01478a5ad976426792873d112f173c677db67d205a22d758defdc83</originalsourceid><addsrcrecordid>eNpdkU1v1DAQhi0EoqVw44wsceHQgD_WH7kgrQKllVpVQnC2JrFTvErsxXYq9ofwf3G3pVo4eTTz6B2_8yL0mpL3nLfkg9_MmRHGRavJE3RMV4w1hEj19KA-Qi9y3pBKMdE-R0ecKs2lJMfo93UYYoDs8FeXS0wu425XYom__ODLDvuAP0GfYHTB901lfC4QCl5zJfD5MkPAV26CEGfAnZumjCFYvB5HN5S87-Arf5Og-BhO8UW4hVyrPdTFKYYdPotp3o9xB1vo_VTXvkTPRpiye_XwnqDvZ5-_defN5fWXi2592QwrpUvD5Kg1aKWA0NoAAbZVcsWkaplW3FLKRqr4IJWyvVSWEQGMWSW0daMdND9BH-91t0s_Ozu4UBJMZpv8DGlnInjz7yT4H-Ym3hpZF-i2rQLvHgRS_LnUC5rZ56G6huDikk09OOGqFfJu19v_0E1cUqj2DBMrLQURVFTq9J4aUsw5ufHxM5SYu7zNYd4Vf3No4BH-GzD_A0Hfp90</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2548650515</pqid></control><display><type>article</type><title>Onconase Restores Cytotoxicity in Dabrafenib-Resistant A375 Human Melanoma Cells and Affects Cell Migration, Invasion and Colony Formation Capability</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>MDPI - Multidisciplinary Digital Publishing Institute</source><source>PubMed Central</source><creator>Raineri, Alice ; Fasoli, Sabrina ; Campagnari, Rachele ; Gotte, Giovanni ; Menegazzi, Marta</creator><creatorcontrib>Raineri, Alice ; Fasoli, Sabrina ; Campagnari, Rachele ; Gotte, Giovanni ; Menegazzi, Marta</creatorcontrib><description>Melanoma is a lethal tumor because of its severe metastatic potential, and serine/threonine-protein kinase B-raf inhibitors (BRAFi) are used in patients harboring BRAF-mutation. Unfortunately, BRAFi induce resistance. Therefore, we tested the activity of onconase (ONC), a cytotoxic RNase variant, against BRAFi-resistant cells to re-establish the efficacy of the chemotherapy. To do so, an A375 dabrafenib-resistant (A375DR) melanoma cell subpopulation was selected and its behavior compared with that of parental (A375P) cells by crystal violet, 5-Bromo-2'-deoxyuridine incorporation, and cleaved poly(ADP-ribose) polymerase 1 (PARP1) western blot measurements. Then, nuclear p65 Nuclear Factor kappaB (NF-κB) and IκB kinases-α/β (IKK) phosphorylation levels were measured. Gelatin zymography was performed to evaluate metalloproteinase 2 (MMP2) activity. In addition, assays to measure migration, invasion and soft agar colony formation were performed to examine the tumor cell dissemination propensity. ONC affected the total viability and the proliferation rate of both A375P and A375DR cell subpopulations in a dose-dependent manner and also induced apoptotic cell death. Among its pleiotropic effects, ONC reduced nuclear p65 NF-κB amount and IKK phosphorylation level, as well as MMP2 activity in both cell subpopulations. ONC decreased cell colony formation, migration, and invasion capability. Notably, it induced apoptosis and inhibited colony formation and invasiveness more extensively in A375DR than in A375P cells. In conclusion, ONC successfully counteracts melanoma malignancy especially in BRAFi-resistant cells and could become a tool against melanoma recurrence.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms20235980</identifier><identifier>PMID: 31783660</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>AKT protein ; Antineoplastic Agents - pharmacology ; Apoptosis ; Apoptosis - drug effects ; Cancer therapies ; Cell adhesion & migration ; Cell death ; Cell growth ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell Proliferation - drug effects ; Chemotherapy ; Colonies ; Cytotoxicity ; Cytotoxins - pharmacology ; Drug dosages ; Drug resistance ; Drug Resistance, Neoplasm - drug effects ; Enzymes ; Gelatin ; Gelatinase A ; Gene Expression Regulation, Neoplastic - drug effects ; Humans ; I-kappa B Kinase - metabolism ; IKK protein ; Imidazoles - pharmacology ; Incorporation ; Invasiveness ; Malignancy ; Matrix Metalloproteinase 2 - metabolism ; Melanoma ; Melanoma - drug therapy ; Melanoma - metabolism ; Mesothelioma ; Metalloproteinase ; Metastases ; Mutation ; Neoplasm Invasiveness - pathology ; NF-kappa B - metabolism ; NF-κB protein ; Oximes - pharmacology ; Phosphorylation ; Poly(ADP-ribose) ; Poly(ADP-ribose) polymerase ; Protein Kinase Inhibitors - pharmacology ; Proteins ; Proto-Oncogene Proteins B-raf - metabolism ; Raf protein ; Ribonucleases - pharmacology ; Ribose ; Signal Transduction - drug effects ; Skin cancer ; Stem Cells - drug effects ; Tumors</subject><ispartof>International journal of molecular sciences, 2019-11, Vol.20 (23), p.5980</ispartof><rights>2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2019 by the authors. 2019</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c478t-26f88a877a01478a5ad976426792873d112f173c677db67d205a22d758defdc83</citedby><cites>FETCH-LOGICAL-c478t-26f88a877a01478a5ad976426792873d112f173c677db67d205a22d758defdc83</cites><orcidid>0000-0003-3179-7158 ; 0000-0003-1310-9227</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/PMC6928899/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6928899/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,883,27907,27908,53774,53776</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31783660$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Raineri, Alice</creatorcontrib><creatorcontrib>Fasoli, Sabrina</creatorcontrib><creatorcontrib>Campagnari, Rachele</creatorcontrib><creatorcontrib>Gotte, Giovanni</creatorcontrib><creatorcontrib>Menegazzi, Marta</creatorcontrib><title>Onconase Restores Cytotoxicity in Dabrafenib-Resistant A375 Human Melanoma Cells and Affects Cell Migration, Invasion and Colony Formation Capability</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><description>Melanoma is a lethal tumor because of its severe metastatic potential, and serine/threonine-protein kinase B-raf inhibitors (BRAFi) are used in patients harboring BRAF-mutation. Unfortunately, BRAFi induce resistance. Therefore, we tested the activity of onconase (ONC), a cytotoxic RNase variant, against BRAFi-resistant cells to re-establish the efficacy of the chemotherapy. To do so, an A375 dabrafenib-resistant (A375DR) melanoma cell subpopulation was selected and its behavior compared with that of parental (A375P) cells by crystal violet, 5-Bromo-2'-deoxyuridine incorporation, and cleaved poly(ADP-ribose) polymerase 1 (PARP1) western blot measurements. Then, nuclear p65 Nuclear Factor kappaB (NF-κB) and IκB kinases-α/β (IKK) phosphorylation levels were measured. Gelatin zymography was performed to evaluate metalloproteinase 2 (MMP2) activity. In addition, assays to measure migration, invasion and soft agar colony formation were performed to examine the tumor cell dissemination propensity. ONC affected the total viability and the proliferation rate of both A375P and A375DR cell subpopulations in a dose-dependent manner and also induced apoptotic cell death. Among its pleiotropic effects, ONC reduced nuclear p65 NF-κB amount and IKK phosphorylation level, as well as MMP2 activity in both cell subpopulations. ONC decreased cell colony formation, migration, and invasion capability. Notably, it induced apoptosis and inhibited colony formation and invasiveness more extensively in A375DR than in A375P cells. In conclusion, ONC successfully counteracts melanoma malignancy especially in BRAFi-resistant cells and could become a tool against melanoma recurrence.</description><subject>AKT protein</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>Cancer therapies</subject><subject>Cell adhesion & migration</subject><subject>Cell death</subject><subject>Cell growth</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Chemotherapy</subject><subject>Colonies</subject><subject>Cytotoxicity</subject><subject>Cytotoxins - pharmacology</subject><subject>Drug dosages</subject><subject>Drug resistance</subject><subject>Drug Resistance, Neoplasm - drug effects</subject><subject>Enzymes</subject><subject>Gelatin</subject><subject>Gelatinase A</subject><subject>Gene Expression Regulation, Neoplastic - drug effects</subject><subject>Humans</subject><subject>I-kappa B Kinase - metabolism</subject><subject>IKK protein</subject><subject>Imidazoles - pharmacology</subject><subject>Incorporation</subject><subject>Invasiveness</subject><subject>Malignancy</subject><subject>Matrix Metalloproteinase 2 - metabolism</subject><subject>Melanoma</subject><subject>Melanoma - drug therapy</subject><subject>Melanoma - metabolism</subject><subject>Mesothelioma</subject><subject>Metalloproteinase</subject><subject>Metastases</subject><subject>Mutation</subject><subject>Neoplasm Invasiveness - pathology</subject><subject>NF-kappa B - metabolism</subject><subject>NF-κB protein</subject><subject>Oximes - pharmacology</subject><subject>Phosphorylation</subject><subject>Poly(ADP-ribose)</subject><subject>Poly(ADP-ribose) polymerase</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins B-raf - metabolism</subject><subject>Raf protein</subject><subject>Ribonucleases - pharmacology</subject><subject>Ribose</subject><subject>Signal Transduction - drug effects</subject><subject>Skin cancer</subject><subject>Stem Cells - drug effects</subject><subject>Tumors</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkU1v1DAQhi0EoqVw44wsceHQgD_WH7kgrQKllVpVQnC2JrFTvErsxXYq9ofwf3G3pVo4eTTz6B2_8yL0mpL3nLfkg9_MmRHGRavJE3RMV4w1hEj19KA-Qi9y3pBKMdE-R0ecKs2lJMfo93UYYoDs8FeXS0wu425XYom__ODLDvuAP0GfYHTB901lfC4QCl5zJfD5MkPAV26CEGfAnZumjCFYvB5HN5S87-Arf5Og-BhO8UW4hVyrPdTFKYYdPotp3o9xB1vo_VTXvkTPRpiye_XwnqDvZ5-_defN5fWXi2592QwrpUvD5Kg1aKWA0NoAAbZVcsWkaplW3FLKRqr4IJWyvVSWEQGMWSW0daMdND9BH-91t0s_Ozu4UBJMZpv8DGlnInjz7yT4H-Ym3hpZF-i2rQLvHgRS_LnUC5rZ56G6huDikk09OOGqFfJu19v_0E1cUqj2DBMrLQURVFTq9J4aUsw5ufHxM5SYu7zNYd4Vf3No4BH-GzD_A0Hfp90</recordid><startdate>20191127</startdate><enddate>20191127</enddate><creator>Raineri, Alice</creator><creator>Fasoli, Sabrina</creator><creator>Campagnari, Rachele</creator><creator>Gotte, Giovanni</creator><creator>Menegazzi, Marta</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>8G5</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>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3179-7158</orcidid><orcidid>https://orcid.org/0000-0003-1310-9227</orcidid></search><sort><creationdate>20191127</creationdate><title>Onconase Restores Cytotoxicity in Dabrafenib-Resistant A375 Human Melanoma Cells and Affects Cell Migration, Invasion and Colony Formation Capability</title><author>Raineri, Alice ; Fasoli, Sabrina ; Campagnari, Rachele ; Gotte, Giovanni ; Menegazzi, Marta</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c478t-26f88a877a01478a5ad976426792873d112f173c677db67d205a22d758defdc83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>AKT protein</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>Cancer therapies</topic><topic>Cell adhesion & migration</topic><topic>Cell death</topic><topic>Cell growth</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Chemotherapy</topic><topic>Colonies</topic><topic>Cytotoxicity</topic><topic>Cytotoxins - pharmacology</topic><topic>Drug dosages</topic><topic>Drug resistance</topic><topic>Drug Resistance, Neoplasm - drug effects</topic><topic>Enzymes</topic><topic>Gelatin</topic><topic>Gelatinase A</topic><topic>Gene Expression Regulation, Neoplastic - drug effects</topic><topic>Humans</topic><topic>I-kappa B Kinase - metabolism</topic><topic>IKK protein</topic><topic>Imidazoles - pharmacology</topic><topic>Incorporation</topic><topic>Invasiveness</topic><topic>Malignancy</topic><topic>Matrix Metalloproteinase 2 - metabolism</topic><topic>Melanoma</topic><topic>Melanoma - drug therapy</topic><topic>Melanoma - metabolism</topic><topic>Mesothelioma</topic><topic>Metalloproteinase</topic><topic>Metastases</topic><topic>Mutation</topic><topic>Neoplasm Invasiveness - pathology</topic><topic>NF-kappa B - metabolism</topic><topic>NF-κB protein</topic><topic>Oximes - pharmacology</topic><topic>Phosphorylation</topic><topic>Poly(ADP-ribose)</topic><topic>Poly(ADP-ribose) polymerase</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins B-raf - metabolism</topic><topic>Raf protein</topic><topic>Ribonucleases - pharmacology</topic><topic>Ribose</topic><topic>Signal Transduction - drug effects</topic><topic>Skin cancer</topic><topic>Stem Cells - drug effects</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Raineri, Alice</creatorcontrib><creatorcontrib>Fasoli, Sabrina</creatorcontrib><creatorcontrib>Campagnari, Rachele</creatorcontrib><creatorcontrib>Gotte, Giovanni</creatorcontrib><creatorcontrib>Menegazzi, Marta</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>Research Library (Alumni Edition)</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 Central Student</collection><collection>Research Library Prep</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Research Library (Corporate)</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>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>International journal of molecular sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Raineri, Alice</au><au>Fasoli, Sabrina</au><au>Campagnari, Rachele</au><au>Gotte, Giovanni</au><au>Menegazzi, Marta</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Onconase Restores Cytotoxicity in Dabrafenib-Resistant A375 Human Melanoma Cells and Affects Cell Migration, Invasion and Colony Formation Capability</atitle><jtitle>International journal of molecular sciences</jtitle><addtitle>Int J Mol Sci</addtitle><date>2019-11-27</date><risdate>2019</risdate><volume>20</volume><issue>23</issue><spage>5980</spage><pages>5980-</pages><issn>1422-0067</issn><issn>1661-6596</issn><eissn>1422-0067</eissn><abstract>Melanoma is a lethal tumor because of its severe metastatic potential, and serine/threonine-protein kinase B-raf inhibitors (BRAFi) are used in patients harboring BRAF-mutation. Unfortunately, BRAFi induce resistance. Therefore, we tested the activity of onconase (ONC), a cytotoxic RNase variant, against BRAFi-resistant cells to re-establish the efficacy of the chemotherapy. To do so, an A375 dabrafenib-resistant (A375DR) melanoma cell subpopulation was selected and its behavior compared with that of parental (A375P) cells by crystal violet, 5-Bromo-2'-deoxyuridine incorporation, and cleaved poly(ADP-ribose) polymerase 1 (PARP1) western blot measurements. Then, nuclear p65 Nuclear Factor kappaB (NF-κB) and IκB kinases-α/β (IKK) phosphorylation levels were measured. Gelatin zymography was performed to evaluate metalloproteinase 2 (MMP2) activity. In addition, assays to measure migration, invasion and soft agar colony formation were performed to examine the tumor cell dissemination propensity. ONC affected the total viability and the proliferation rate of both A375P and A375DR cell subpopulations in a dose-dependent manner and also induced apoptotic cell death. Among its pleiotropic effects, ONC reduced nuclear p65 NF-κB amount and IKK phosphorylation level, as well as MMP2 activity in both cell subpopulations. ONC decreased cell colony formation, migration, and invasion capability. Notably, it induced apoptosis and inhibited colony formation and invasiveness more extensively in A375DR than in A375P cells. In conclusion, ONC successfully counteracts melanoma malignancy especially in BRAFi-resistant cells and could become a tool against melanoma recurrence.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>31783660</pmid><doi>10.3390/ijms20235980</doi><orcidid>https://orcid.org/0000-0003-3179-7158</orcidid><orcidid>https://orcid.org/0000-0003-1310-9227</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1422-0067 |
| ispartof | International journal of molecular sciences, 2019-11, Vol.20 (23), p.5980 |
| issn | 1422-0067 1661-6596 1422-0067 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_6928899 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; MDPI - Multidisciplinary Digital Publishing Institute; PubMed Central |
| subjects | AKT protein Antineoplastic Agents - pharmacology Apoptosis Apoptosis - drug effects Cancer therapies Cell adhesion & migration Cell death Cell growth Cell Line, Tumor Cell Movement - drug effects Cell Proliferation - drug effects Chemotherapy Colonies Cytotoxicity Cytotoxins - pharmacology Drug dosages Drug resistance Drug Resistance, Neoplasm - drug effects Enzymes Gelatin Gelatinase A Gene Expression Regulation, Neoplastic - drug effects Humans I-kappa B Kinase - metabolism IKK protein Imidazoles - pharmacology Incorporation Invasiveness Malignancy Matrix Metalloproteinase 2 - metabolism Melanoma Melanoma - drug therapy Melanoma - metabolism Mesothelioma Metalloproteinase Metastases Mutation Neoplasm Invasiveness - pathology NF-kappa B - metabolism NF-κB protein Oximes - pharmacology Phosphorylation Poly(ADP-ribose) Poly(ADP-ribose) polymerase Protein Kinase Inhibitors - pharmacology Proteins Proto-Oncogene Proteins B-raf - metabolism Raf protein Ribonucleases - pharmacology Ribose Signal Transduction - drug effects Skin cancer Stem Cells - drug effects Tumors |
| title | Onconase Restores Cytotoxicity in Dabrafenib-Resistant A375 Human Melanoma Cells and Affects Cell Migration, Invasion and Colony Formation Capability |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-16T21%3A04%3A21IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Onconase%20Restores%20Cytotoxicity%20in%20Dabrafenib-Resistant%20A375%20Human%20Melanoma%20Cells%20and%20Affects%20Cell%20Migration,%20Invasion%20and%20Colony%20Formation%20Capability&rft.jtitle=International%20journal%20of%20molecular%20sciences&rft.au=Raineri,%20Alice&rft.date=2019-11-27&rft.volume=20&rft.issue=23&rft.spage=5980&rft.pages=5980-&rft.issn=1422-0067&rft.eissn=1422-0067&rft_id=info:doi/10.3390/ijms20235980&rft_dat=%3Cproquest_pubme%3E2548650515%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2548650515&rft_id=info:pmid/31783660&rfr_iscdi=true |