Potential Role of GST-π in Lung Cancer Stem Cell Cisplatin Resistance
Background. Cancer stem cells (CSCs) are responsible for tumorigenesis, chemoresistance, and metastasis. Chemoresistance is a major challenge in the management of lung cancer. Glutathione-sulphur-transferase-π (GST-π) plays an important role in the origin and development of various types of cancer b...
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| description | Background. Cancer stem cells (CSCs) are responsible for tumorigenesis, chemoresistance, and metastasis. Chemoresistance is a major challenge in the management of lung cancer. Glutathione-sulphur-transferase-π (GST-π) plays an important role in the origin and development of various types of cancer by regulating the cellular redox balance. Recent investigations have demonstrated that GST-π is associated with the chemoresistance of lung CSCs (LCSCs). However, the mechanism of GST-π in lung cancer, particularly in LCSCs, remains unclear. The present study is aimed at exploring the potential role of GST-π in stemness and cisplatin (DDP) resistance of LCSCs. Materials and methods. In the present study, lung cancer cell spheres were established using the A549 cell line, which according to our previous research, was confirmed to exhibit characteristics of stem cells. Next, GST-π protein expression, apoptosis percentage, and intracellular reactive oxygen species (ROS) concentration in A549 adherent cells and A549 cell spheres were analyzed by western blotting and flow cytometry, respectively. Finally, DDP resistance, ROS concentration, and GST-π expression in LCSCs were analyzed following the interference with GST-π using DL-buthionine-(S,R)-sulphoximine and N-acetylcysteine. Results. The results revealed that GST-π was highly expressed in A549 cell spheres compared with A549 adherent cells and was associated with a decreased intracellular ROS concentration (both P |
| doi_str_mv | 10.1155/2021/9142364 |
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Cancer stem cells (CSCs) are responsible for tumorigenesis, chemoresistance, and metastasis. Chemoresistance is a major challenge in the management of lung cancer. Glutathione-sulphur-transferase-π (GST-π) plays an important role in the origin and development of various types of cancer by regulating the cellular redox balance. Recent investigations have demonstrated that GST-π is associated with the chemoresistance of lung CSCs (LCSCs). However, the mechanism of GST-π in lung cancer, particularly in LCSCs, remains unclear. The present study is aimed at exploring the potential role of GST-π in stemness and cisplatin (DDP) resistance of LCSCs. Materials and methods. In the present study, lung cancer cell spheres were established using the A549 cell line, which according to our previous research, was confirmed to exhibit characteristics of stem cells. Next, GST-π protein expression, apoptosis percentage, and intracellular reactive oxygen species (ROS) concentration in A549 adherent cells and A549 cell spheres were analyzed by western blotting and flow cytometry, respectively. Finally, DDP resistance, ROS concentration, and GST-π expression in LCSCs were analyzed following the interference with GST-π using DL-buthionine-(S,R)-sulphoximine and N-acetylcysteine. Results. The results revealed that GST-π was highly expressed in A549 cell spheres compared with A549 adherent cells and was associated with a decreased intracellular ROS concentration (both P<0.05). Regulating GST-π protein expression could alter DDP resistance of LCSCs by influencing ROS. Conclusion. These results suggested that GST-π may be important for LCSC drug resistance by downregulating ROS levels. These findings may contribute to the development of new adjuvant therapeutic strategies for lung cancer.</description><identifier>ISSN: 2314-6133</identifier><identifier>EISSN: 2314-6141</identifier><identifier>DOI: 10.1155/2021/9142364</identifier><identifier>PMID: 34840986</identifier><language>eng</language><publisher>United States: Hindawi</publisher><subject>A549 Cells ; Acetylcysteine ; Adherent cells ; Antineoplastic Agents - pharmacology ; Apoptosis ; Autophagy ; Biomedical research ; Cancer therapies ; Chemoresistance ; Chemotherapy ; Cisplatin ; Cisplatin - pharmacology ; Cloning ; Drug resistance ; Drug Resistance, Neoplasm - physiology ; Flow cytometry ; Glutathione ; Glutathione S-Transferase pi - metabolism ; Humans ; Intracellular ; Lung cancer ; Lung Neoplasms - drug therapy ; Lung Neoplasms - metabolism ; Medical research ; Metabolism ; Metastases ; Mitochondrial DNA ; Neoplastic Stem Cells - drug effects ; Neoplastic Stem Cells - metabolism ; Peptides ; Pharmaceuticals ; Polyclonal antibodies ; Proteins ; Reactive oxygen species ; Reactive Oxygen Species - metabolism ; Spheres ; Spheroids, Cellular - drug effects ; Spheroids, Cellular - metabolism ; Stem cells ; Sulfur ; Tumorigenesis ; Western blotting</subject><ispartof>BioMed research international, 2021, Vol.2021, p.9142364-11</ispartof><rights>Copyright © 2021 Wenjun Wang et al.</rights><rights>Copyright © 2021 Wenjun Wang et al. This is an open access article distributed under the Creative Commons Attribution License (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License. https://creativecommons.org/licenses/by/4.0</rights><rights>Copyright © 2021 Wenjun Wang et al. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c448t-3d94d8eaf1cbefefa4b7118220c9966896594a7d92d87d136119309aefa828ea3</citedby><cites>FETCH-LOGICAL-c448t-3d94d8eaf1cbefefa4b7118220c9966896594a7d92d87d136119309aefa828ea3</cites><orcidid>0000-0001-5596-6636 ; 0000-0001-8585-6374</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/PMC8626171/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626171/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,4024,27923,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34840986$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Rhim, Taiyoun</contributor><contributor>Taiyoun Rhim</contributor><creatorcontrib>Wang, Wenjun</creatorcontrib><creatorcontrib>Wei, Jianping</creatorcontrib><creatorcontrib>Tu, Xiaoyun</creatorcontrib><creatorcontrib>Ye, Xiaoqun</creatorcontrib><title>Potential Role of GST-π in Lung Cancer Stem Cell Cisplatin Resistance</title><title>BioMed research international</title><addtitle>Biomed Res Int</addtitle><description>Background. Cancer stem cells (CSCs) are responsible for tumorigenesis, chemoresistance, and metastasis. Chemoresistance is a major challenge in the management of lung cancer. Glutathione-sulphur-transferase-π (GST-π) plays an important role in the origin and development of various types of cancer by regulating the cellular redox balance. Recent investigations have demonstrated that GST-π is associated with the chemoresistance of lung CSCs (LCSCs). However, the mechanism of GST-π in lung cancer, particularly in LCSCs, remains unclear. The present study is aimed at exploring the potential role of GST-π in stemness and cisplatin (DDP) resistance of LCSCs. Materials and methods. In the present study, lung cancer cell spheres were established using the A549 cell line, which according to our previous research, was confirmed to exhibit characteristics of stem cells. Next, GST-π protein expression, apoptosis percentage, and intracellular reactive oxygen species (ROS) concentration in A549 adherent cells and A549 cell spheres were analyzed by western blotting and flow cytometry, respectively. Finally, DDP resistance, ROS concentration, and GST-π expression in LCSCs were analyzed following the interference with GST-π using DL-buthionine-(S,R)-sulphoximine and N-acetylcysteine. Results. The results revealed that GST-π was highly expressed in A549 cell spheres compared with A549 adherent cells and was associated with a decreased intracellular ROS concentration (both P<0.05). Regulating GST-π protein expression could alter DDP resistance of LCSCs by influencing ROS. Conclusion. These results suggested that GST-π may be important for LCSC drug resistance by downregulating ROS levels. These findings may contribute to the development of new adjuvant therapeutic strategies for lung cancer.</description><subject>A549 Cells</subject><subject>Acetylcysteine</subject><subject>Adherent cells</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis</subject><subject>Autophagy</subject><subject>Biomedical research</subject><subject>Cancer therapies</subject><subject>Chemoresistance</subject><subject>Chemotherapy</subject><subject>Cisplatin</subject><subject>Cisplatin - pharmacology</subject><subject>Cloning</subject><subject>Drug resistance</subject><subject>Drug Resistance, Neoplasm - physiology</subject><subject>Flow cytometry</subject><subject>Glutathione</subject><subject>Glutathione S-Transferase pi - metabolism</subject><subject>Humans</subject><subject>Intracellular</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - drug therapy</subject><subject>Lung Neoplasms - metabolism</subject><subject>Medical research</subject><subject>Metabolism</subject><subject>Metastases</subject><subject>Mitochondrial DNA</subject><subject>Neoplastic Stem Cells - drug effects</subject><subject>Neoplastic Stem Cells - metabolism</subject><subject>Peptides</subject><subject>Pharmaceuticals</subject><subject>Polyclonal antibodies</subject><subject>Proteins</subject><subject>Reactive oxygen species</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Spheres</subject><subject>Spheroids, Cellular - drug effects</subject><subject>Spheroids, Cellular - metabolism</subject><subject>Stem cells</subject><subject>Sulfur</subject><subject>Tumorigenesis</subject><subject>Western blotting</subject><issn>2314-6133</issn><issn>2314-6141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>RHX</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>eNp9kUFLxDAQhYMoKro3zxLwImg1k6TZ5CJIcVVYUFY9h2ybaqTbrE2rePMf-pdM2XVRD-YygffNYx4PoT0gJwBpekoJhVMFnDLB19A2ZcATARzWV3_GttAghGcSnwRBlNhEW4xLTpQU22h061tbt85UeOIri32JL-_uk88P7Go87upHnJk6tw2-a-0MZ7aqcObCvDJt1Cc2uND2-i7aKE0V7GA5d9DD6OI-u0rGN5fX2fk4yTmXbcIKxQtpTQn51Ja2NHw6BJCUklwpIaQSqeJmWChayGEBTAAoRpSJpKRxj-2gs4XvvJvObJHH0xtT6XnjZqZ51944_Vup3ZN-9K9aCipgCNHgcGnQ-JfOhlbPXMhjLFNb3wVNBeE8BUF79OAP-uy7po7xeoqlKhVSRup4QeWND6Gx5eoYILrvSPcd6WVHEd__GWAFfzcSgaMF8OTqwry5_-2-ADhjl4Y</recordid><startdate>2021</startdate><enddate>2021</enddate><creator>Wang, Wenjun</creator><creator>Wei, Jianping</creator><creator>Tu, Xiaoyun</creator><creator>Ye, Xiaoqun</creator><general>Hindawi</general><general>Hindawi Limited</general><scope>RHU</scope><scope>RHW</scope><scope>RHX</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>3V.</scope><scope>7QL</scope><scope>7QO</scope><scope>7T7</scope><scope>7TK</scope><scope>7U7</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>CWDGH</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-5596-6636</orcidid><orcidid>https://orcid.org/0000-0001-8585-6374</orcidid></search><sort><creationdate>2021</creationdate><title>Potential Role of GST-π in Lung Cancer Stem Cell Cisplatin Resistance</title><author>Wang, Wenjun ; Wei, Jianping ; Tu, Xiaoyun ; Ye, Xiaoqun</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c448t-3d94d8eaf1cbefefa4b7118220c9966896594a7d92d87d136119309aefa828ea3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>A549 Cells</topic><topic>Acetylcysteine</topic><topic>Adherent cells</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis</topic><topic>Autophagy</topic><topic>Biomedical research</topic><topic>Cancer therapies</topic><topic>Chemoresistance</topic><topic>Chemotherapy</topic><topic>Cisplatin</topic><topic>Cisplatin - pharmacology</topic><topic>Cloning</topic><topic>Drug resistance</topic><topic>Drug Resistance, Neoplasm - physiology</topic><topic>Flow cytometry</topic><topic>Glutathione</topic><topic>Glutathione S-Transferase pi - metabolism</topic><topic>Humans</topic><topic>Intracellular</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - drug therapy</topic><topic>Lung Neoplasms - metabolism</topic><topic>Medical research</topic><topic>Metabolism</topic><topic>Metastases</topic><topic>Mitochondrial DNA</topic><topic>Neoplastic Stem Cells - drug effects</topic><topic>Neoplastic Stem Cells - metabolism</topic><topic>Peptides</topic><topic>Pharmaceuticals</topic><topic>Polyclonal antibodies</topic><topic>Proteins</topic><topic>Reactive oxygen species</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Spheres</topic><topic>Spheroids, Cellular - drug effects</topic><topic>Spheroids, Cellular - metabolism</topic><topic>Stem cells</topic><topic>Sulfur</topic><topic>Tumorigenesis</topic><topic>Western blotting</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Wenjun</creatorcontrib><creatorcontrib>Wei, Jianping</creatorcontrib><creatorcontrib>Tu, Xiaoyun</creatorcontrib><creatorcontrib>Ye, Xiaoqun</creatorcontrib><collection>Hindawi Publishing Complete</collection><collection>Hindawi Publishing Subscription Journals</collection><collection>Hindawi Publishing Open Access Journals</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 Central (Corporate)</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Industrial and Applied Microbiology Abstracts (Microbiology A)</collection><collection>Neurosciences Abstracts</collection><collection>Toxicology Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</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>Advanced Technologies & Aerospace Collection</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Technology Collection</collection><collection>Natural Science Collection</collection><collection>Environmental Sciences and Pollution Management</collection><collection>ProQuest One Community College</collection><collection>Middle East & Africa Database</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</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>BioMed research international</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Wenjun</au><au>Wei, Jianping</au><au>Tu, Xiaoyun</au><au>Ye, Xiaoqun</au><au>Rhim, Taiyoun</au><au>Taiyoun Rhim</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Potential Role of GST-π in Lung Cancer Stem Cell Cisplatin Resistance</atitle><jtitle>BioMed research international</jtitle><addtitle>Biomed Res Int</addtitle><date>2021</date><risdate>2021</risdate><volume>2021</volume><spage>9142364</spage><epage>11</epage><pages>9142364-11</pages><issn>2314-6133</issn><eissn>2314-6141</eissn><abstract>Background. Cancer stem cells (CSCs) are responsible for tumorigenesis, chemoresistance, and metastasis. Chemoresistance is a major challenge in the management of lung cancer. Glutathione-sulphur-transferase-π (GST-π) plays an important role in the origin and development of various types of cancer by regulating the cellular redox balance. Recent investigations have demonstrated that GST-π is associated with the chemoresistance of lung CSCs (LCSCs). However, the mechanism of GST-π in lung cancer, particularly in LCSCs, remains unclear. The present study is aimed at exploring the potential role of GST-π in stemness and cisplatin (DDP) resistance of LCSCs. Materials and methods. In the present study, lung cancer cell spheres were established using the A549 cell line, which according to our previous research, was confirmed to exhibit characteristics of stem cells. Next, GST-π protein expression, apoptosis percentage, and intracellular reactive oxygen species (ROS) concentration in A549 adherent cells and A549 cell spheres were analyzed by western blotting and flow cytometry, respectively. Finally, DDP resistance, ROS concentration, and GST-π expression in LCSCs were analyzed following the interference with GST-π using DL-buthionine-(S,R)-sulphoximine and N-acetylcysteine. Results. The results revealed that GST-π was highly expressed in A549 cell spheres compared with A549 adherent cells and was associated with a decreased intracellular ROS concentration (both P<0.05). Regulating GST-π protein expression could alter DDP resistance of LCSCs by influencing ROS. Conclusion. These results suggested that GST-π may be important for LCSC drug resistance by downregulating ROS levels. These findings may contribute to the development of new adjuvant therapeutic strategies for lung cancer.</abstract><cop>United States</cop><pub>Hindawi</pub><pmid>34840986</pmid><doi>10.1155/2021/9142364</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-5596-6636</orcidid><orcidid>https://orcid.org/0000-0001-8585-6374</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | A549 Cells Acetylcysteine Adherent cells Antineoplastic Agents - pharmacology Apoptosis Autophagy Biomedical research Cancer therapies Chemoresistance Chemotherapy Cisplatin Cisplatin - pharmacology Cloning Drug resistance Drug Resistance, Neoplasm - physiology Flow cytometry Glutathione Glutathione S-Transferase pi - metabolism Humans Intracellular Lung cancer Lung Neoplasms - drug therapy Lung Neoplasms - metabolism Medical research Metabolism Metastases Mitochondrial DNA Neoplastic Stem Cells - drug effects Neoplastic Stem Cells - metabolism Peptides Pharmaceuticals Polyclonal antibodies Proteins Reactive oxygen species Reactive Oxygen Species - metabolism Spheres Spheroids, Cellular - drug effects Spheroids, Cellular - metabolism Stem cells Sulfur Tumorigenesis Western blotting |
| title | Potential Role of GST-π in Lung Cancer Stem Cell Cisplatin Resistance |
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