Axolotl extract induces cell cycle arrest and differentiation in human acute myeloid leukemia HL-60 cells
Acute myeloid leukemia is the most common form of acute leukemia in adults, constituting about 80% of cases. Although remarkable progress has been made in the therapeutic scenario for patients with acute myeloid leukemia, research and development of new and effective anticancer agents to improve pat...
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2020-09-01
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| Series: | Tumor Biology |
| Online Access: | https://doi.org/10.1177/1010428320954735 |
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| author | Sherif Suleiman Riccardo Di Fiore Analisse Cassar Melissa Marie Formosa Pierre Schembri-Wismayer Jean Calleja-Agius |
| author_facet | Sherif Suleiman Riccardo Di Fiore Analisse Cassar Melissa Marie Formosa Pierre Schembri-Wismayer Jean Calleja-Agius |
| author_sort | Sherif Suleiman |
| collection | DOAJ |
| description | Acute myeloid leukemia is the most common form of acute leukemia in adults, constituting about 80% of cases. Although remarkable progress has been made in the therapeutic scenario for patients with acute myeloid leukemia, research and development of new and effective anticancer agents to improve patient outcome and minimize toxicity is needed. In this study, the antitumor activity of axolotl (AXO) Ambystoma mexicanum crude extract was assessed in vitro on the human acute myeloid leukemia HL-60 cell line. The anticancer activity was evaluated in terms of ability to influence proliferative activity, cell viability, cell cycle arrest, and differentiation. Moreover, gene expression analysis was performed to evaluate the genes involved in the regulation of these processes. The AXO crude extract exhibited antiproliferative but not cytotoxic activities on HL-60 cells, with cell cycle arrest in the G0/G1 phase. Furthermore, the AXO-treated HL-60 cells showed an increase in both the percentage of nitroblue tetrazolium positive cells and the expression of CD11b, whereas the proportion of CD14-positive cells did not change, suggesting that extract is able to induce differentiation toward the granulocytic lineage. Finally, the treatment with AXO extract caused upregulation of CEBPA, CEBPB, CEBPE, SPI1, CDKN1A , and CDKN2C , and downregulation of c-MYC . Our data clearly show the potential anticancer activity of Ambystoma mexicanum on HL-60 cells and suggest that it could help develop promising therapeutic agents for the treatment of acute myeloid leukemia. |
| format | Article |
| id | doaj-art-e601f453af054dc58b7c7dd0a69382e6 |
| institution | Kabale University |
| issn | 1423-0380 |
| language | English |
| publishDate | 2020-09-01 |
| publisher | SAGE Publishing |
| record_format | Article |
| series | Tumor Biology |
| spelling | doaj-art-e601f453af054dc58b7c7dd0a69382e62025-08-20T03:38:44ZengSAGE PublishingTumor Biology1423-03802020-09-014210.1177/1010428320954735Axolotl extract induces cell cycle arrest and differentiation in human acute myeloid leukemia HL-60 cellsSherif Suleiman0Riccardo Di Fiore1Analisse Cassar2Melissa Marie Formosa3Pierre Schembri-Wismayer4Jean Calleja-Agius5Department of Anatomy, Faculty of Medicine and Surgery, University of Malta, Msida, MaltaSbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, College of Science and Technology, Temple University, Philadelphia, PA, USADepartment of Anatomy, Faculty of Medicine and Surgery, University of Malta, Msida, MaltaDepartment of Applied Biomedical Science, Faculty of Health Sciences, University of Malta, Msida, MaltaDepartment of Anatomy, Faculty of Medicine and Surgery, University of Malta, Msida, MaltaDepartment of Anatomy, Faculty of Medicine and Surgery, University of Malta, Msida, MaltaAcute myeloid leukemia is the most common form of acute leukemia in adults, constituting about 80% of cases. Although remarkable progress has been made in the therapeutic scenario for patients with acute myeloid leukemia, research and development of new and effective anticancer agents to improve patient outcome and minimize toxicity is needed. In this study, the antitumor activity of axolotl (AXO) Ambystoma mexicanum crude extract was assessed in vitro on the human acute myeloid leukemia HL-60 cell line. The anticancer activity was evaluated in terms of ability to influence proliferative activity, cell viability, cell cycle arrest, and differentiation. Moreover, gene expression analysis was performed to evaluate the genes involved in the regulation of these processes. The AXO crude extract exhibited antiproliferative but not cytotoxic activities on HL-60 cells, with cell cycle arrest in the G0/G1 phase. Furthermore, the AXO-treated HL-60 cells showed an increase in both the percentage of nitroblue tetrazolium positive cells and the expression of CD11b, whereas the proportion of CD14-positive cells did not change, suggesting that extract is able to induce differentiation toward the granulocytic lineage. Finally, the treatment with AXO extract caused upregulation of CEBPA, CEBPB, CEBPE, SPI1, CDKN1A , and CDKN2C , and downregulation of c-MYC . Our data clearly show the potential anticancer activity of Ambystoma mexicanum on HL-60 cells and suggest that it could help develop promising therapeutic agents for the treatment of acute myeloid leukemia.https://doi.org/10.1177/1010428320954735 |
| spellingShingle | Sherif Suleiman Riccardo Di Fiore Analisse Cassar Melissa Marie Formosa Pierre Schembri-Wismayer Jean Calleja-Agius Axolotl extract induces cell cycle arrest and differentiation in human acute myeloid leukemia HL-60 cells Tumor Biology |
| title | Axolotl extract induces cell cycle arrest and differentiation in human acute myeloid leukemia HL-60 cells |
| title_full | Axolotl extract induces cell cycle arrest and differentiation in human acute myeloid leukemia HL-60 cells |
| title_fullStr | Axolotl extract induces cell cycle arrest and differentiation in human acute myeloid leukemia HL-60 cells |
| title_full_unstemmed | Axolotl extract induces cell cycle arrest and differentiation in human acute myeloid leukemia HL-60 cells |
| title_short | Axolotl extract induces cell cycle arrest and differentiation in human acute myeloid leukemia HL-60 cells |
| title_sort | axolotl extract induces cell cycle arrest and differentiation in human acute myeloid leukemia hl 60 cells |
| url | https://doi.org/10.1177/1010428320954735 |
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