A Novel Chalcone Derivative Regulates the Expression and Phosphorylation of ERK1/2 by Inhibiting Fli-1 Promoter Activity for Preventing the Malignant Progression of Erythroleukemia
Acute erythroleukemia is a rare form of acute myeloid leukemia recognized by its distinct phenotypic attribute of erythroblasts proliferation. In this study, in vitro experiments showed that a newly synthesized chalcone (ZH-254) inhibited cell proliferation, caused apoptosis, arrested the cell cycle...
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MDPI AG
2022-12-01
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| author | Min Mo Youfen Ma Jia Yu Mashaal Ahmad Xinwei Wan Zijiang Yu Bixue Xu Heng Luo |
| author_facet | Min Mo Youfen Ma Jia Yu Mashaal Ahmad Xinwei Wan Zijiang Yu Bixue Xu Heng Luo |
| author_sort | Min Mo |
| collection | DOAJ |
| description | Acute erythroleukemia is a rare form of acute myeloid leukemia recognized by its distinct phenotypic attribute of erythroblasts proliferation. In this study, in vitro experiments showed that a newly synthesized chalcone (ZH-254) inhibited cell proliferation, caused apoptosis, arrested the cell cycle in the G1 phase, and downregulated Fli-1 expression by inhibiting Fli-1 promoter activity. In vivo experiments showed that ZH-254 could effectively alleviate splenomegaly and prolong the survival of erythroleukemia mice. RT-PCR and Western blot analysis showed that ZH-254 could regulate the expression of Fli-1 target genes and G1-phase-related cell cycle proteins, including Rb, Bcl-2, Bax, ERK1/2, Gata-1, P110, SHIP-1, p-ERK1, CDK4, C-myc, Cyclin D1, Smad-3, GSK-3, and p21. Among them, the compound most significantly regulated the expression and phosphorylation of ERK1, the target gene of Fli-1 involved in regulating cell proliferation and apoptosis. Thus, ZH-254 restricts the malignancy of erythroleukemia by causing the inactivation of Fli-1 expression via suppressing its promoter activity, further regulating the expression and phosphorylation of ERK1- and G1-phase-related genes. These results reveal the critical role of Fli-1 in the growth and survival of various hematological malignancies and point to chalcone derivatives as lead compounds for the development of anti-Fli-1 drugs for the treatment of erythroleukemia with overexpression of Fli-1. |
| first_indexed | 2024-03-09T13:15:53Z |
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| language | English |
| last_indexed | 2024-03-09T13:15:53Z |
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| spelling | doaj.art-ce347a71608d4afd81944bd15f347fac2023-11-30T21:36:59ZengMDPI AGCatalysts2073-43442022-12-011318410.3390/catal13010084A Novel Chalcone Derivative Regulates the Expression and Phosphorylation of ERK1/2 by Inhibiting Fli-1 Promoter Activity for Preventing the Malignant Progression of ErythroleukemiaMin Mo0Youfen Ma1Jia Yu2Mashaal Ahmad3Xinwei Wan4Zijiang Yu5Bixue Xu6Heng Luo7Department of Anatomy, School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550025, ChinaState Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, ChinaState Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, ChinaState Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, ChinaState Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, ChinaDepartment of Anatomy, School of Basic Medical Sciences, Guizhou Medical University, Guiyang 550025, ChinaState Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, ChinaState Key Laboratory for Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, ChinaAcute erythroleukemia is a rare form of acute myeloid leukemia recognized by its distinct phenotypic attribute of erythroblasts proliferation. In this study, in vitro experiments showed that a newly synthesized chalcone (ZH-254) inhibited cell proliferation, caused apoptosis, arrested the cell cycle in the G1 phase, and downregulated Fli-1 expression by inhibiting Fli-1 promoter activity. In vivo experiments showed that ZH-254 could effectively alleviate splenomegaly and prolong the survival of erythroleukemia mice. RT-PCR and Western blot analysis showed that ZH-254 could regulate the expression of Fli-1 target genes and G1-phase-related cell cycle proteins, including Rb, Bcl-2, Bax, ERK1/2, Gata-1, P110, SHIP-1, p-ERK1, CDK4, C-myc, Cyclin D1, Smad-3, GSK-3, and p21. Among them, the compound most significantly regulated the expression and phosphorylation of ERK1, the target gene of Fli-1 involved in regulating cell proliferation and apoptosis. Thus, ZH-254 restricts the malignancy of erythroleukemia by causing the inactivation of Fli-1 expression via suppressing its promoter activity, further regulating the expression and phosphorylation of ERK1- and G1-phase-related genes. These results reveal the critical role of Fli-1 in the growth and survival of various hematological malignancies and point to chalcone derivatives as lead compounds for the development of anti-Fli-1 drugs for the treatment of erythroleukemia with overexpression of Fli-1.https://www.mdpi.com/2073-4344/13/1/84chalconeFli-1apoptosis inductioncell-cycle arrestleukemia inhibition |
| spellingShingle | Min Mo Youfen Ma Jia Yu Mashaal Ahmad Xinwei Wan Zijiang Yu Bixue Xu Heng Luo A Novel Chalcone Derivative Regulates the Expression and Phosphorylation of ERK1/2 by Inhibiting Fli-1 Promoter Activity for Preventing the Malignant Progression of Erythroleukemia Catalysts chalcone Fli-1 apoptosis induction cell-cycle arrest leukemia inhibition |
| title | A Novel Chalcone Derivative Regulates the Expression and Phosphorylation of ERK1/2 by Inhibiting Fli-1 Promoter Activity for Preventing the Malignant Progression of Erythroleukemia |
| title_full | A Novel Chalcone Derivative Regulates the Expression and Phosphorylation of ERK1/2 by Inhibiting Fli-1 Promoter Activity for Preventing the Malignant Progression of Erythroleukemia |
| title_fullStr | A Novel Chalcone Derivative Regulates the Expression and Phosphorylation of ERK1/2 by Inhibiting Fli-1 Promoter Activity for Preventing the Malignant Progression of Erythroleukemia |
| title_full_unstemmed | A Novel Chalcone Derivative Regulates the Expression and Phosphorylation of ERK1/2 by Inhibiting Fli-1 Promoter Activity for Preventing the Malignant Progression of Erythroleukemia |
| title_short | A Novel Chalcone Derivative Regulates the Expression and Phosphorylation of ERK1/2 by Inhibiting Fli-1 Promoter Activity for Preventing the Malignant Progression of Erythroleukemia |
| title_sort | novel chalcone derivative regulates the expression and phosphorylation of erk1 2 by inhibiting fli 1 promoter activity for preventing the malignant progression of erythroleukemia |
| topic | chalcone Fli-1 apoptosis induction cell-cycle arrest leukemia inhibition |
| url | https://www.mdpi.com/2073-4344/13/1/84 |
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