NBDHEX re‐sensitizes adriamycin‐resistant breast cancer by inhibiting glutathione S‐transferase pi
Abstract Purpose Adriamycin is a novel chemotherapeutic agent of great benefit for treating breast cancer. However, adriamycin ‐resistance remains a major obstacle. The vital Glutathione transferase P1 (GSTPi) inhibitor 6‐(7‐nitro‐2,1,3‐benzoxadiazol‐4‐ylthio) hexanol (NBDHEX) has recently shown ant...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-03-01
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| Series: | Cancer Medicine |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/cam4.5370 |
| _version_ | 1797866838420357120 |
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| author | Huanhuan Sha Renrui Zou Ya Lu Yujie Gan Rong Ma Jifeng Feng Dan Chen |
| author_facet | Huanhuan Sha Renrui Zou Ya Lu Yujie Gan Rong Ma Jifeng Feng Dan Chen |
| author_sort | Huanhuan Sha |
| collection | DOAJ |
| description | Abstract Purpose Adriamycin is a novel chemotherapeutic agent of great benefit for treating breast cancer. However, adriamycin ‐resistance remains a major obstacle. The vital Glutathione transferase P1 (GSTPi) inhibitor 6‐(7‐nitro‐2,1,3‐benzoxadiazol‐4‐ylthio) hexanol (NBDHEX) has recently shown antitumor activity in various cancers. In this study, we analyzed the effect of NBDHEX and adriamycin combination against breast cancer in vitro and in vivo. Methods CCK‐8 assay was performed to test cell viability. The location and expression level of GSTpi was determined by immunofluorescence and Western blot in cells and immunohistochemistry staining in tissues. The enzyme activity test was applied to detect the effect of NBDHEX on the activity of GSTpi. The apoptosis related proteins' expression was tested using Western blot. The phosphorylation sites of GSTpi were detected by mass spectrometry. Antitumor effects of single treatment or co‐administration of adriamycin and NBDHEX were evaluated in nude mice. Results NBDHEX treatment inhibited GSTpi enzyme activity and co‐administration of adriamycin and NBDHEX promoted apoptosis of adriamycin‐resistance breast cancer cell. Moreover, drug combination of NBDHEX and adriamycin significantly enhanced tumor growth inhibition compared with single agent. Conclusion NBDHEX serves as a good candidate for combination with adriamycin, offering new insights for breast cancer treatment. |
| first_indexed | 2024-04-09T23:31:46Z |
| format | Article |
| id | doaj.art-63b45c0f6e29413ca5de1b4916116567 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-09T23:31:46Z |
| publishDate | 2023-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-63b45c0f6e29413ca5de1b49161165672023-03-21T05:20:40ZengWileyCancer Medicine2045-76342023-03-011255833584510.1002/cam4.5370NBDHEX re‐sensitizes adriamycin‐resistant breast cancer by inhibiting glutathione S‐transferase piHuanhuan Sha0Renrui Zou1Ya Lu2Yujie Gan3Rong Ma4Jifeng Feng5Dan Chen6Department of Chemotherapy Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research Nanjing Jiangsu ChinaThe Fourth Clinical School of The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research Nanjing Jiangsu ChinaThe Fourth Clinical School of The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research Nanjing Jiangsu ChinaThe Fourth Clinical School of The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research Nanjing Jiangsu ChinaResearch Center of Clinical Oncology, Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research Nanjing Jiangsu ChinaThe Fourth Clinical School of The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research Nanjing Jiangsu ChinaResearch Center of Clinical Oncology, Jiangsu Cancer Hospital, The Affiliated Cancer Hospital of Nanjing Medical University, Jiangsu Institute of Cancer Research Nanjing Jiangsu ChinaAbstract Purpose Adriamycin is a novel chemotherapeutic agent of great benefit for treating breast cancer. However, adriamycin ‐resistance remains a major obstacle. The vital Glutathione transferase P1 (GSTPi) inhibitor 6‐(7‐nitro‐2,1,3‐benzoxadiazol‐4‐ylthio) hexanol (NBDHEX) has recently shown antitumor activity in various cancers. In this study, we analyzed the effect of NBDHEX and adriamycin combination against breast cancer in vitro and in vivo. Methods CCK‐8 assay was performed to test cell viability. The location and expression level of GSTpi was determined by immunofluorescence and Western blot in cells and immunohistochemistry staining in tissues. The enzyme activity test was applied to detect the effect of NBDHEX on the activity of GSTpi. The apoptosis related proteins' expression was tested using Western blot. The phosphorylation sites of GSTpi were detected by mass spectrometry. Antitumor effects of single treatment or co‐administration of adriamycin and NBDHEX were evaluated in nude mice. Results NBDHEX treatment inhibited GSTpi enzyme activity and co‐administration of adriamycin and NBDHEX promoted apoptosis of adriamycin‐resistance breast cancer cell. Moreover, drug combination of NBDHEX and adriamycin significantly enhanced tumor growth inhibition compared with single agent. Conclusion NBDHEX serves as a good candidate for combination with adriamycin, offering new insights for breast cancer treatment.https://doi.org/10.1002/cam4.5370adriamycinbreast cancerGSTpiNBDHEXresistant |
| spellingShingle | Huanhuan Sha Renrui Zou Ya Lu Yujie Gan Rong Ma Jifeng Feng Dan Chen NBDHEX re‐sensitizes adriamycin‐resistant breast cancer by inhibiting glutathione S‐transferase pi Cancer Medicine adriamycin breast cancer GSTpi NBDHEX resistant |
| title | NBDHEX re‐sensitizes adriamycin‐resistant breast cancer by inhibiting glutathione S‐transferase pi |
| title_full | NBDHEX re‐sensitizes adriamycin‐resistant breast cancer by inhibiting glutathione S‐transferase pi |
| title_fullStr | NBDHEX re‐sensitizes adriamycin‐resistant breast cancer by inhibiting glutathione S‐transferase pi |
| title_full_unstemmed | NBDHEX re‐sensitizes adriamycin‐resistant breast cancer by inhibiting glutathione S‐transferase pi |
| title_short | NBDHEX re‐sensitizes adriamycin‐resistant breast cancer by inhibiting glutathione S‐transferase pi |
| title_sort | nbdhex re sensitizes adriamycin resistant breast cancer by inhibiting glutathione s transferase pi |
| topic | adriamycin breast cancer GSTpi NBDHEX resistant |
| url | https://doi.org/10.1002/cam4.5370 |
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