Trifluoperazine induces cellular apoptosis by inhibiting autophagy and targeting NUPR1 in multiple myeloma
Multiple myeloma (MM) is the second most common hematologic malignancy of immunoglobulin‐secreting plasma cells. Recent modern combination therapies have improved survival rates, but many patients develop resistance to novel drugs, leading to relapse. Trifluoperazine (TFP), a typical antipsychotic d...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-10-01
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| Series: | FEBS Open Bio |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/2211-5463.12960 |
| _version_ | 1828174619756986368 |
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| author | Anmao Li Xuanxin Chen Zizi Jing Jianbin Chen |
| author_facet | Anmao Li Xuanxin Chen Zizi Jing Jianbin Chen |
| author_sort | Anmao Li |
| collection | DOAJ |
| description | Multiple myeloma (MM) is the second most common hematologic malignancy of immunoglobulin‐secreting plasma cells. Recent modern combination therapies have improved survival rates, but many patients develop resistance to novel drugs, leading to relapse. Trifluoperazine (TFP), a typical antipsychotic drug, has been reported to exert antitumor effects by targeting various pathways. Thus far, the role of TFP in MM has not been elucidated. In the current study, we demonstrated that TFP inhibited cell growth and autophagy activity but induced apoptosis of U266 and RPMI 8226 MM cells. Furthermore, cotreatment of these cell lines with TFP and rapamycin, a potent autophagy inducer, reduced cell apoptosis compared with TFP treatment alone. We also found that TFP inhibited nuclear protein 1 (NUPR1) expression. In the presence of TFP, cells stably overexpressing NUPR1 showed a higher viability than cells treated with the nonspecific control. Autophagy suppression and apoptosis induction caused by TFP were also reversed in MM cells upon NUPR1 overexpression. Overall, our results indicate that in the context of MM, TFP targets NUPR1, inhibiting cell growth and inducing apoptosis by autophagy inhibition. Our results could contribute toward efforts for the development of more effective therapies for MM to be tested in future clinical trials. |
| first_indexed | 2024-04-12T04:15:39Z |
| format | Article |
| id | doaj.art-642fc25d382d4ee6816bf22ac0231f26 |
| institution | Directory Open Access Journal |
| issn | 2211-5463 |
| language | English |
| last_indexed | 2024-04-12T04:15:39Z |
| publishDate | 2020-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | FEBS Open Bio |
| spelling | doaj.art-642fc25d382d4ee6816bf22ac0231f262022-12-22T03:48:25ZengWileyFEBS Open Bio2211-54632020-10-0110102097210610.1002/2211-5463.12960Trifluoperazine induces cellular apoptosis by inhibiting autophagy and targeting NUPR1 in multiple myelomaAnmao Li0Xuanxin Chen1Zizi Jing2Jianbin Chen3Department of Hematology the First Affiliated Hospital of Chongqing Medical University Yuzhong ChinaDepartment of Hematology the First Affiliated Hospital of Chongqing Medical University Yuzhong ChinaDepartment of Hematology the First Affiliated Hospital of Chongqing Medical University Yuzhong ChinaDepartment of Hematology the First Affiliated Hospital of Chongqing Medical University Yuzhong ChinaMultiple myeloma (MM) is the second most common hematologic malignancy of immunoglobulin‐secreting plasma cells. Recent modern combination therapies have improved survival rates, but many patients develop resistance to novel drugs, leading to relapse. Trifluoperazine (TFP), a typical antipsychotic drug, has been reported to exert antitumor effects by targeting various pathways. Thus far, the role of TFP in MM has not been elucidated. In the current study, we demonstrated that TFP inhibited cell growth and autophagy activity but induced apoptosis of U266 and RPMI 8226 MM cells. Furthermore, cotreatment of these cell lines with TFP and rapamycin, a potent autophagy inducer, reduced cell apoptosis compared with TFP treatment alone. We also found that TFP inhibited nuclear protein 1 (NUPR1) expression. In the presence of TFP, cells stably overexpressing NUPR1 showed a higher viability than cells treated with the nonspecific control. Autophagy suppression and apoptosis induction caused by TFP were also reversed in MM cells upon NUPR1 overexpression. Overall, our results indicate that in the context of MM, TFP targets NUPR1, inhibiting cell growth and inducing apoptosis by autophagy inhibition. Our results could contribute toward efforts for the development of more effective therapies for MM to be tested in future clinical trials.https://doi.org/10.1002/2211-5463.12960apoptosisautophagymultiple myelomanuclear protein 1trifluoperazine |
| spellingShingle | Anmao Li Xuanxin Chen Zizi Jing Jianbin Chen Trifluoperazine induces cellular apoptosis by inhibiting autophagy and targeting NUPR1 in multiple myeloma FEBS Open Bio apoptosis autophagy multiple myeloma nuclear protein 1 trifluoperazine |
| title | Trifluoperazine induces cellular apoptosis by inhibiting autophagy and targeting NUPR1 in multiple myeloma |
| title_full | Trifluoperazine induces cellular apoptosis by inhibiting autophagy and targeting NUPR1 in multiple myeloma |
| title_fullStr | Trifluoperazine induces cellular apoptosis by inhibiting autophagy and targeting NUPR1 in multiple myeloma |
| title_full_unstemmed | Trifluoperazine induces cellular apoptosis by inhibiting autophagy and targeting NUPR1 in multiple myeloma |
| title_short | Trifluoperazine induces cellular apoptosis by inhibiting autophagy and targeting NUPR1 in multiple myeloma |
| title_sort | trifluoperazine induces cellular apoptosis by inhibiting autophagy and targeting nupr1 in multiple myeloma |
| topic | apoptosis autophagy multiple myeloma nuclear protein 1 trifluoperazine |
| url | https://doi.org/10.1002/2211-5463.12960 |
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