Intracellular levels of reactive oxygen species correlate with ABT‐263 sensitivity in non‐small‐cell lung cancer cells
ABT‐263 (Navitoclax) is a BH3‐mimetic drugs targeting anti‐apoptotic B‐cell lymphoma‐2 (BCL‐2) family proteins, including BCL‐2, BCL‐xL, and BCL‐w, thereby inducing apoptosis. In small‐cell lung cancer (SCLC) cells, the response to ABT‐263 is associated with the expression of myeloid cell leukemia‐1...
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| Veröffentlicht in: | Cancer science 2020-10, Vol.111 (10), p.3793-3801 |
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| creator | Ohgino, Keiko Terai, Hideki Yasuda, Hiroyuki Nukaga, Shigenari Hamamoto, Junko Tani, Tetsuo Kuroda, Aoi Arai, Daisuke Ishioka, Kota Masuzawa, Keita Ikemura, Shinnosuke Kawada, Ichiro Naoki, Katsuhiko Fukunaga, Koichi Soejima, Kenzo |
| description | ABT‐263 (Navitoclax) is a BH3‐mimetic drugs targeting anti‐apoptotic B‐cell lymphoma‐2 (BCL‐2) family proteins, including BCL‐2, BCL‐xL, and BCL‐w, thereby inducing apoptosis. In small‐cell lung cancer (SCLC) cells, the response to ABT‐263 is associated with the expression of myeloid cell leukemia‐1 (MCL‐1) protein, however the efficacy of ABT‐263 in non‐small‐cell lung cancer (NSCLC) has not been thoroughly evaluated. There are currently no established biomarkers for predicting the efficacy of ABT‐263 treatment in NSCLC. We screened a panel of different NSCLC cell lines and found that ABT‐263 inhibited cell proliferation and induced apoptosis in Calu‐1, Calu‐3, and BID007 cells. Inconsistent with previous reports on SCLC, low levels of MCL‐1 did not predict the response to ABT‐263 in NSCLC cells, however we found that intracellular levels of reactive oxygen species (ROS) in cancer cells were associated with sensitivity to ABT‐263 in NSCLC cells. We also showed that increasing the level of intracellular ROS could enhance the sensitivity to ABT‐263 in NSCLC cells. In summary, we propose that the intracellular levels of ROS could be used as a potential novel biomarker for predicting a response to ABT‐263 in NSCLC. Furthermore, we show some evidence supporting the further assessment of ABT‐263 as a new therapeutic strategy in patients with NSCLC combined with agents regulating ROS levels. We believe that our findings and follow‐up studies on this matter would lead to novel diagnostic and treatment strategies in patients with NSCLC.
This article clarified the potential relationship between intracellular ROS and sensitivity to BH3‐mimetic drug, ABT‐263 in non‐small‐cell lung cancer. |
| doi_str_mv | 10.1111/cas.14569 |
| format | Article |
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This article clarified the potential relationship between intracellular ROS and sensitivity to BH3‐mimetic drug, ABT‐263 in non‐small‐cell lung cancer.</description><identifier>ISSN: 1347-9032</identifier><identifier>EISSN: 1349-7006</identifier><identifier>DOI: 10.1111/cas.14569</identifier><identifier>PMID: 32687646</identifier><language>eng</language><publisher>England: John Wiley & Sons, Inc</publisher><subject>ABT‐263 ; Aniline Compounds - pharmacology ; Antibiotics ; Antibodies ; Antineoplastic Agents - pharmacology ; Apoptosis ; Apoptosis - drug effects ; BCL‐2 inhibitor ; Biomarkers ; Carcinoma, Non-Small-Cell Lung - etiology ; Carcinoma, Non-Small-Cell Lung - metabolism ; Cell adhesion & migration ; Cell Line, Tumor ; Cell proliferation ; Dose-Response Relationship, Drug ; Drug delivery ; Drug Discovery and Delivery ; Drug Resistance, Neoplasm - genetics ; Flow cytometry ; Gene expression ; Gene Silencing ; Humans ; Intracellular ; Intracellular levels ; Intracellular Space ; Lung cancer ; Lung Neoplasms - etiology ; Lung Neoplasms - metabolism ; Lymphoma ; navitoclax ; Non-small cell lung carcinoma ; non‐small‐cell lung cancer ; Original ; Oxidation-Reduction ; Penicillin ; Proteins ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; RNA, Small Interfering - genetics ; Sulfonamides - pharmacology</subject><ispartof>Cancer science, 2020-10, Vol.111 (10), p.3793-3801</ispartof><rights>2020 The Authors. published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.</rights><rights>2020. This work is published under http://creativecommons.org/licenses/by-nc/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><cites>FETCH-LOGICAL-c3929-ddd6b08fbed8a0f6b9df6de76ebae534453879d0f14b0b256afa404ce86622203</cites><orcidid>0000-0002-1118-1930</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/PMC7541018/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7541018/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,1417,11562,27924,27925,45574,45575,46052,46476,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32687646$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ohgino, Keiko</creatorcontrib><creatorcontrib>Terai, Hideki</creatorcontrib><creatorcontrib>Yasuda, Hiroyuki</creatorcontrib><creatorcontrib>Nukaga, Shigenari</creatorcontrib><creatorcontrib>Hamamoto, Junko</creatorcontrib><creatorcontrib>Tani, Tetsuo</creatorcontrib><creatorcontrib>Kuroda, Aoi</creatorcontrib><creatorcontrib>Arai, Daisuke</creatorcontrib><creatorcontrib>Ishioka, Kota</creatorcontrib><creatorcontrib>Masuzawa, Keita</creatorcontrib><creatorcontrib>Ikemura, Shinnosuke</creatorcontrib><creatorcontrib>Kawada, Ichiro</creatorcontrib><creatorcontrib>Naoki, Katsuhiko</creatorcontrib><creatorcontrib>Fukunaga, Koichi</creatorcontrib><creatorcontrib>Soejima, Kenzo</creatorcontrib><title>Intracellular levels of reactive oxygen species correlate with ABT‐263 sensitivity in non‐small‐cell lung cancer cells</title><title>Cancer science</title><addtitle>Cancer Sci</addtitle><description>ABT‐263 (Navitoclax) is a BH3‐mimetic drugs targeting anti‐apoptotic B‐cell lymphoma‐2 (BCL‐2) family proteins, including BCL‐2, BCL‐xL, and BCL‐w, thereby inducing apoptosis. In small‐cell lung cancer (SCLC) cells, the response to ABT‐263 is associated with the expression of myeloid cell leukemia‐1 (MCL‐1) protein, however the efficacy of ABT‐263 in non‐small‐cell lung cancer (NSCLC) has not been thoroughly evaluated. There are currently no established biomarkers for predicting the efficacy of ABT‐263 treatment in NSCLC. We screened a panel of different NSCLC cell lines and found that ABT‐263 inhibited cell proliferation and induced apoptosis in Calu‐1, Calu‐3, and BID007 cells. Inconsistent with previous reports on SCLC, low levels of MCL‐1 did not predict the response to ABT‐263 in NSCLC cells, however we found that intracellular levels of reactive oxygen species (ROS) in cancer cells were associated with sensitivity to ABT‐263 in NSCLC cells. We also showed that increasing the level of intracellular ROS could enhance the sensitivity to ABT‐263 in NSCLC cells. In summary, we propose that the intracellular levels of ROS could be used as a potential novel biomarker for predicting a response to ABT‐263 in NSCLC. Furthermore, we show some evidence supporting the further assessment of ABT‐263 as a new therapeutic strategy in patients with NSCLC combined with agents regulating ROS levels. We believe that our findings and follow‐up studies on this matter would lead to novel diagnostic and treatment strategies in patients with NSCLC.
This article clarified the potential relationship between intracellular ROS and sensitivity to BH3‐mimetic drug, ABT‐263 in non‐small‐cell lung cancer.</description><subject>ABT‐263</subject><subject>Aniline Compounds - pharmacology</subject><subject>Antibiotics</subject><subject>Antibodies</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Apoptosis - drug effects</subject><subject>BCL‐2 inhibitor</subject><subject>Biomarkers</subject><subject>Carcinoma, Non-Small-Cell Lung - etiology</subject><subject>Carcinoma, Non-Small-Cell Lung - metabolism</subject><subject>Cell adhesion & migration</subject><subject>Cell Line, Tumor</subject><subject>Cell proliferation</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug delivery</subject><subject>Drug Discovery and Delivery</subject><subject>Drug Resistance, Neoplasm - genetics</subject><subject>Flow cytometry</subject><subject>Gene expression</subject><subject>Gene Silencing</subject><subject>Humans</subject><subject>Intracellular</subject><subject>Intracellular levels</subject><subject>Intracellular Space</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - etiology</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lymphoma</subject><subject>navitoclax</subject><subject>Non-small cell lung carcinoma</subject><subject>non‐small‐cell lung cancer</subject><subject>Original</subject><subject>Oxidation-Reduction</subject><subject>Penicillin</subject><subject>Proteins</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>RNA, Small Interfering - genetics</subject><subject>Sulfonamides - pharmacology</subject><issn>1347-9032</issn><issn>1349-7006</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNp1kc1u3CAUhVGVqPlpF3mBCCmrLpxgwNhsKk1GTRspUhdJ1gjj6wkRA1OwZzpSF32EPmOfpDiTRO2ibC669_Cdiw5CJyU5L_O5MDqdl7wS8g06LBmXRU2I2Hu614UkjB6go5QeCWGCS_4WHTAqmlpwcYh-XPshagPOjU5H7GANLuHQ4wjaDHYNOHzfLsDjtAJjIWETYgSnB8AbOzzg2eXd75-_qGA4gU82v7DDFluPffB5kJbauVwnA-xGv8BGewMRT430Du332iV4_1yP0f3Vp7v5l-Lm6-fr-eymMExSWXRdJ1rS9C10jSa9aGXXiw5qAa2GinFesaaWHelL3pKWVkL3mhNuoBGCUkrYMfq4467GdgmdgenPTq2iXeq4VUFb9e_E2we1CGtVV7wkZZMBZ8-AGL6NkAb1GMbo886Kct5ITqmcbD7sVCaGlCL0rw4lUVNQKgelnoLK2tO_V3pVviSTBRc7wcY62P6fpOaz2x3yD6sQoww</recordid><startdate>202010</startdate><enddate>202010</enddate><creator>Ohgino, Keiko</creator><creator>Terai, Hideki</creator><creator>Yasuda, Hiroyuki</creator><creator>Nukaga, Shigenari</creator><creator>Hamamoto, Junko</creator><creator>Tani, Tetsuo</creator><creator>Kuroda, Aoi</creator><creator>Arai, Daisuke</creator><creator>Ishioka, Kota</creator><creator>Masuzawa, Keita</creator><creator>Ikemura, Shinnosuke</creator><creator>Kawada, Ichiro</creator><creator>Naoki, Katsuhiko</creator><creator>Fukunaga, Koichi</creator><creator>Soejima, Kenzo</creator><general>John Wiley & Sons, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</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>8FE</scope><scope>8FH</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>LK8</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-1118-1930</orcidid></search><sort><creationdate>202010</creationdate><title>Intracellular levels of reactive oxygen species correlate with ABT‐263 sensitivity in non‐small‐cell lung cancer cells</title><author>Ohgino, Keiko ; Terai, Hideki ; Yasuda, Hiroyuki ; Nukaga, Shigenari ; Hamamoto, Junko ; Tani, Tetsuo ; Kuroda, Aoi ; Arai, Daisuke ; Ishioka, Kota ; Masuzawa, Keita ; Ikemura, Shinnosuke ; Kawada, Ichiro ; Naoki, Katsuhiko ; Fukunaga, Koichi ; Soejima, Kenzo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3929-ddd6b08fbed8a0f6b9df6de76ebae534453879d0f14b0b256afa404ce86622203</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>ABT‐263</topic><topic>Aniline Compounds - pharmacology</topic><topic>Antibiotics</topic><topic>Antibodies</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Apoptosis - drug effects</topic><topic>BCL‐2 inhibitor</topic><topic>Biomarkers</topic><topic>Carcinoma, Non-Small-Cell Lung - etiology</topic><topic>Carcinoma, Non-Small-Cell Lung - metabolism</topic><topic>Cell adhesion & migration</topic><topic>Cell Line, Tumor</topic><topic>Cell proliferation</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug delivery</topic><topic>Drug Discovery and Delivery</topic><topic>Drug Resistance, Neoplasm - genetics</topic><topic>Flow cytometry</topic><topic>Gene expression</topic><topic>Gene Silencing</topic><topic>Humans</topic><topic>Intracellular</topic><topic>Intracellular levels</topic><topic>Intracellular Space</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - etiology</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lymphoma</topic><topic>navitoclax</topic><topic>Non-small cell lung carcinoma</topic><topic>non‐small‐cell lung cancer</topic><topic>Original</topic><topic>Oxidation-Reduction</topic><topic>Penicillin</topic><topic>Proteins</topic><topic>Reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>RNA, Small Interfering - genetics</topic><topic>Sulfonamides - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ohgino, Keiko</creatorcontrib><creatorcontrib>Terai, Hideki</creatorcontrib><creatorcontrib>Yasuda, Hiroyuki</creatorcontrib><creatorcontrib>Nukaga, Shigenari</creatorcontrib><creatorcontrib>Hamamoto, Junko</creatorcontrib><creatorcontrib>Tani, Tetsuo</creatorcontrib><creatorcontrib>Kuroda, Aoi</creatorcontrib><creatorcontrib>Arai, Daisuke</creatorcontrib><creatorcontrib>Ishioka, Kota</creatorcontrib><creatorcontrib>Masuzawa, Keita</creatorcontrib><creatorcontrib>Ikemura, Shinnosuke</creatorcontrib><creatorcontrib>Kawada, Ichiro</creatorcontrib><creatorcontrib>Naoki, Katsuhiko</creatorcontrib><creatorcontrib>Fukunaga, Koichi</creatorcontrib><creatorcontrib>Soejima, Kenzo</creatorcontrib><collection>Wiley Online Library Open Access</collection><collection>Wiley Online Library (Open Access Collection)</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Biological Science 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>PubMed Central (Full Participant titles)</collection><jtitle>Cancer science</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ohgino, Keiko</au><au>Terai, Hideki</au><au>Yasuda, Hiroyuki</au><au>Nukaga, Shigenari</au><au>Hamamoto, Junko</au><au>Tani, Tetsuo</au><au>Kuroda, Aoi</au><au>Arai, Daisuke</au><au>Ishioka, Kota</au><au>Masuzawa, Keita</au><au>Ikemura, Shinnosuke</au><au>Kawada, Ichiro</au><au>Naoki, Katsuhiko</au><au>Fukunaga, Koichi</au><au>Soejima, Kenzo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Intracellular levels of reactive oxygen species correlate with ABT‐263 sensitivity in non‐small‐cell lung cancer cells</atitle><jtitle>Cancer science</jtitle><addtitle>Cancer Sci</addtitle><date>2020-10</date><risdate>2020</risdate><volume>111</volume><issue>10</issue><spage>3793</spage><epage>3801</epage><pages>3793-3801</pages><issn>1347-9032</issn><eissn>1349-7006</eissn><abstract>ABT‐263 (Navitoclax) is a BH3‐mimetic drugs targeting anti‐apoptotic B‐cell lymphoma‐2 (BCL‐2) family proteins, including BCL‐2, BCL‐xL, and BCL‐w, thereby inducing apoptosis. In small‐cell lung cancer (SCLC) cells, the response to ABT‐263 is associated with the expression of myeloid cell leukemia‐1 (MCL‐1) protein, however the efficacy of ABT‐263 in non‐small‐cell lung cancer (NSCLC) has not been thoroughly evaluated. There are currently no established biomarkers for predicting the efficacy of ABT‐263 treatment in NSCLC. We screened a panel of different NSCLC cell lines and found that ABT‐263 inhibited cell proliferation and induced apoptosis in Calu‐1, Calu‐3, and BID007 cells. Inconsistent with previous reports on SCLC, low levels of MCL‐1 did not predict the response to ABT‐263 in NSCLC cells, however we found that intracellular levels of reactive oxygen species (ROS) in cancer cells were associated with sensitivity to ABT‐263 in NSCLC cells. We also showed that increasing the level of intracellular ROS could enhance the sensitivity to ABT‐263 in NSCLC cells. In summary, we propose that the intracellular levels of ROS could be used as a potential novel biomarker for predicting a response to ABT‐263 in NSCLC. Furthermore, we show some evidence supporting the further assessment of ABT‐263 as a new therapeutic strategy in patients with NSCLC combined with agents regulating ROS levels. We believe that our findings and follow‐up studies on this matter would lead to novel diagnostic and treatment strategies in patients with NSCLC.
This article clarified the potential relationship between intracellular ROS and sensitivity to BH3‐mimetic drug, ABT‐263 in non‐small‐cell lung cancer.</abstract><cop>England</cop><pub>John Wiley & Sons, Inc</pub><pmid>32687646</pmid><doi>10.1111/cas.14569</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-1118-1930</orcidid><oa>free_for_read</oa></addata></record> |
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| ispartof | Cancer science, 2020-10, Vol.111 (10), p.3793-3801 |
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| source | Wiley Online Library - AutoHoldings Journals; MEDLINE; DOAJ Directory of Open Access Journals; Wiley Online Library Open Access; PubMed Central |
| subjects | ABT‐263 Aniline Compounds - pharmacology Antibiotics Antibodies Antineoplastic Agents - pharmacology Apoptosis Apoptosis - drug effects BCL‐2 inhibitor Biomarkers Carcinoma, Non-Small-Cell Lung - etiology Carcinoma, Non-Small-Cell Lung - metabolism Cell adhesion & migration Cell Line, Tumor Cell proliferation Dose-Response Relationship, Drug Drug delivery Drug Discovery and Delivery Drug Resistance, Neoplasm - genetics Flow cytometry Gene expression Gene Silencing Humans Intracellular Intracellular levels Intracellular Space Lung cancer Lung Neoplasms - etiology Lung Neoplasms - metabolism Lymphoma navitoclax Non-small cell lung carcinoma non‐small‐cell lung cancer Original Oxidation-Reduction Penicillin Proteins Reactive oxygen species Reactive Oxygen Species - metabolism RNA, Small Interfering - genetics Sulfonamides - pharmacology |
| title | Intracellular levels of reactive oxygen species correlate with ABT‐263 sensitivity in non‐small‐cell lung cancer cells |
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