Alantolactone inhibits cell autophagy and promotes apoptosis via AP2M1 in acute lymphoblastic leukemia
Abstract Background Acute lymphoblastic leukemia (ALL) is an aggressive hematopoietic malignancy that is most commonly observed in children. Alantolactone (ALT) has been reported to exhibit anti-tumor activity in different types of cancer. The aim of the present study was to investigate the anti-tum...
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| Format: | Article |
| Language: | English |
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BMC
2020-09-01
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| Series: | Cancer Cell International |
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| Online Access: | http://link.springer.com/article/10.1186/s12935-020-01537-9 |
| _version_ | 1828486710368927744 |
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| author | Ce Shi Wenjia Lan Zhenkun Wang Dongguang Yang Jia Wei Zhiyu Liu Yueqiu Teng Mengmeng Gu Tian Yuan Fenglin Cao Jin Zhou Yang Li |
| author_facet | Ce Shi Wenjia Lan Zhenkun Wang Dongguang Yang Jia Wei Zhiyu Liu Yueqiu Teng Mengmeng Gu Tian Yuan Fenglin Cao Jin Zhou Yang Li |
| author_sort | Ce Shi |
| collection | DOAJ |
| description | Abstract Background Acute lymphoblastic leukemia (ALL) is an aggressive hematopoietic malignancy that is most commonly observed in children. Alantolactone (ALT) has been reported to exhibit anti-tumor activity in different types of cancer. The aim of the present study was to investigate the anti-tumor activity and molecular mechanism of ALT in ALL. Methods ALL cell lines were treated with 1, 5 and 10 μM ALT, and cell viability was assessed using an MTT assay and RNA sequencing. Flow cytometry, JC-1 staining and immunofluorescence staining assays were used to measure cell apoptosis and autophagy. Additionally, western blot analysis was used to detect expression of apoptosis and autophagy related proteins. Finally, the effects of ALT on tumor growth were assessed in a BV173 xenograft nude mouse model. Results ALT inhibited the proliferation of ALL cells in a dose-dependent manner. Additionally, it was demonstrated that ALT inhibited cell proliferation, colony formation, autophagy, induced apoptosis and reduced tumor growth in vivo through upregulating the expression of adaptor related protein complex 2 subunit mu 1 (AP2M1). Moreover, the autophagy activator rapamycin, attenuated the pro-apoptotic effects of ALT on BV173 and NALM6 cell lines. Overexpression of AP2M1 decreased the expression of Beclin1 and the LC3-II/LC3-1 ratio, and increased p62 expression. Knockdown of Beclin1 increased the levels of bax, cleaved caspase 3 and cytochrome C, and decreased bcl-2 expression. Conclusions The present study demonstrated that ALT exerts anti-tumor activity through inducing apoptosis and inhibiting autophagy by upregulating AP2M1 in ALL, highlighting a potential therapeutic strategy for treatment of ALL. |
| first_indexed | 2024-12-11T09:37:56Z |
| format | Article |
| id | doaj.art-2d867b38219a45c2931cda0799d88daf |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-11T09:37:56Z |
| publishDate | 2020-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-2d867b38219a45c2931cda0799d88daf2022-12-22T01:12:46ZengBMCCancer Cell International1475-28672020-09-0120111210.1186/s12935-020-01537-9Alantolactone inhibits cell autophagy and promotes apoptosis via AP2M1 in acute lymphoblastic leukemiaCe Shi0Wenjia Lan1Zhenkun Wang2Dongguang Yang3Jia Wei4Zhiyu Liu5Yueqiu Teng6Mengmeng Gu7Tian Yuan8Fenglin Cao9Jin Zhou10Yang Li11Central Laboratory of Hematology and Oncology, The First Affiliated Hospital, Harbin Medical UniversityCentral Laboratory of Hematology and Oncology, The First Affiliated Hospital, Harbin Medical UniversityCentral Laboratory of Hematology and Oncology, The First Affiliated Hospital, Harbin Medical UniversityCentral Laboratory of Hematology and Oncology, The First Affiliated Hospital, Harbin Medical UniversityCentral Laboratory of Hematology and Oncology, The First Affiliated Hospital, Harbin Medical UniversityCentral Laboratory of Hematology and Oncology, The First Affiliated Hospital, Harbin Medical UniversityCentral Laboratory of Hematology and Oncology, The First Affiliated Hospital, Harbin Medical UniversityDepartment of Hematology, The First Affiliated Hospital, Harbin Medical UniversityDepartment of Hematology, Tianjin Medical University Cancer Institute and HospitalCentral Laboratory of Hematology and Oncology, The First Affiliated Hospital, Harbin Medical UniversityDepartment of Hematology, The First Affiliated Hospital, Harbin Medical UniversityCentral Laboratory of Hematology and Oncology, The First Affiliated Hospital, Harbin Medical UniversityAbstract Background Acute lymphoblastic leukemia (ALL) is an aggressive hematopoietic malignancy that is most commonly observed in children. Alantolactone (ALT) has been reported to exhibit anti-tumor activity in different types of cancer. The aim of the present study was to investigate the anti-tumor activity and molecular mechanism of ALT in ALL. Methods ALL cell lines were treated with 1, 5 and 10 μM ALT, and cell viability was assessed using an MTT assay and RNA sequencing. Flow cytometry, JC-1 staining and immunofluorescence staining assays were used to measure cell apoptosis and autophagy. Additionally, western blot analysis was used to detect expression of apoptosis and autophagy related proteins. Finally, the effects of ALT on tumor growth were assessed in a BV173 xenograft nude mouse model. Results ALT inhibited the proliferation of ALL cells in a dose-dependent manner. Additionally, it was demonstrated that ALT inhibited cell proliferation, colony formation, autophagy, induced apoptosis and reduced tumor growth in vivo through upregulating the expression of adaptor related protein complex 2 subunit mu 1 (AP2M1). Moreover, the autophagy activator rapamycin, attenuated the pro-apoptotic effects of ALT on BV173 and NALM6 cell lines. Overexpression of AP2M1 decreased the expression of Beclin1 and the LC3-II/LC3-1 ratio, and increased p62 expression. Knockdown of Beclin1 increased the levels of bax, cleaved caspase 3 and cytochrome C, and decreased bcl-2 expression. Conclusions The present study demonstrated that ALT exerts anti-tumor activity through inducing apoptosis and inhibiting autophagy by upregulating AP2M1 in ALL, highlighting a potential therapeutic strategy for treatment of ALL.http://link.springer.com/article/10.1186/s12935-020-01537-9AlantolactoneAcute lymphoblastic leukemiaAdaptor related protein complex 2 subunit mu 1AutophagyApoptosis |
| spellingShingle | Ce Shi Wenjia Lan Zhenkun Wang Dongguang Yang Jia Wei Zhiyu Liu Yueqiu Teng Mengmeng Gu Tian Yuan Fenglin Cao Jin Zhou Yang Li Alantolactone inhibits cell autophagy and promotes apoptosis via AP2M1 in acute lymphoblastic leukemia Cancer Cell International Alantolactone Acute lymphoblastic leukemia Adaptor related protein complex 2 subunit mu 1 Autophagy Apoptosis |
| title | Alantolactone inhibits cell autophagy and promotes apoptosis via AP2M1 in acute lymphoblastic leukemia |
| title_full | Alantolactone inhibits cell autophagy and promotes apoptosis via AP2M1 in acute lymphoblastic leukemia |
| title_fullStr | Alantolactone inhibits cell autophagy and promotes apoptosis via AP2M1 in acute lymphoblastic leukemia |
| title_full_unstemmed | Alantolactone inhibits cell autophagy and promotes apoptosis via AP2M1 in acute lymphoblastic leukemia |
| title_short | Alantolactone inhibits cell autophagy and promotes apoptosis via AP2M1 in acute lymphoblastic leukemia |
| title_sort | alantolactone inhibits cell autophagy and promotes apoptosis via ap2m1 in acute lymphoblastic leukemia |
| topic | Alantolactone Acute lymphoblastic leukemia Adaptor related protein complex 2 subunit mu 1 Autophagy Apoptosis |
| url | http://link.springer.com/article/10.1186/s12935-020-01537-9 |
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