Transcriptomic Profiles of MV4-11 and Kasumi 1 Acute Myeloid Leukemia Cell Lines Modulated by Epigenetic Modifiers Trichostatin A and 5-Azacytidine

Asmaa, Mat Jusoh Siti; Al‐Jamal, Hamid Ali Nagi; Hussein, Adil; Yahaya, Badrul Hisham; Husin, Azlan; Hassan, Rosline; Hussain, Faezahtul Arbaeyah; Shamsuddin, Shaharum; Johan, Muhammad Farid

doi:10.18502/ijhoscr.v14i1.2362

Cited by 5 publications

(10 citation statements)

References 48 publications

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“…Therefore, it suggested that JOA induces monocyte/macrophages differentiation of THP-1 cells, and activates the phagosome pathway. The result is in accordance with that phagosome pathway was commonly activated in both MV4-11 and Kasumi-1 AML cell lines treated with differentiation inducers, trichostatin A and 5-azacytidine (33).…”

Section: Discussionsupporting

confidence: 90%

Jiyuan Oridonin A Overcomes Differentiation Blockade in Acute Myeloid Leukemia Cells With MLL Rearrangements via Multiple Signaling Pathways

Duan

Zhao

et al. 2021

Front. Oncol.

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Differentiation therapy with all-trans-retinoic acid (ATRA) in acute promyelocytic leukemia (APL), a subtype of acute myeloid leukemia (AML), has been extremely successful in inducing clinical remission in APL patients. However, the differentiation therapy of ATRA-based treatment has not been effective in other subtypes of AML. In this study, we evaluated a small molecule of ent-kaurene diterpenoid, Jiyuan oridonin A (JOA), on the differentiation blockade in AML cells with the mixed lineage leukemia (MLL) gene rearrangements (MLLr) in MV4-11, MOLM-13 and THP-1 cells. We found that JOA could significantly inhibit the proliferation of MOLM-13, MV4-11 and THP-1 cells. Moreover, JOA promoted cell differentiation coupled with cell-cycle exit at G0/G1 and inhibited the colony- forming capacity of these cells. We showed that the anti-proliferative effect of JOA attributed to cell differentiation is most likely through the martens tretinoin response up pathway in the MOLM-13 cell line, and the hematopoietic cell lineage pathway by the inhibition of c-KIT expression and cell adhesion pathway in the THP-1 cell line. Our findings suggest that JOA could be a novel therapeutic agent against human MLLr acute myeloid leukemia.

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Section: Discussionsupporting

confidence: 90%

Jiyuan Oridonin A Overcomes Differentiation Blockade in Acute Myeloid Leukemia Cells With MLL Rearrangements via Multiple Signaling Pathways

Duan

Zhao

et al. 2021

Front. Oncol.

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“…Aberrant methylation of TSGs is involved in the pathogenesis of several cancers [7]. The expression of TSGs, such as the JAK/STAT-negative regulator genes, is silenced due to hypermethylation of the CpG islands in promoter regions, leading to the malignant transformation of normal hematopoietic cells and the development of leukemia [7,8]. Different levels of DNA methylation have been implicated in the development and prognosis of AML [8].…”

Section: Discussionmentioning

confidence: 99%

“…Epigenetic silencing of tumor suppressor genes (TSGs) by DNA hypermethylation has a critical role in the development of leukaemia, including AML [7,8]. Unlike genetic dysregulation, the epigenetic alterations are reversible, making them attractive targets for anticancer therapy.…”

Section: Introductionmentioning

confidence: 99%

“…However, the different methylation status of CpG islands of SOCS-1 has been identified in AML [16][17][18]. The restoration of SHP-1, SOCS-1, and SOCS-3 expression by epigenetic modulating agents such as 5-azacytidine (5-Aza) was associated with significant inhibition of JAK2/STAT3 and STAT5 signaling in AML leukemia cells [8,12]. However, the response rate of the conventional DNA hypomethylating agents is low [19,20].…”

Section: Introductionmentioning

confidence: 99%

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Thymoquinone Inhibits Growth of Acute Myeloid Leukemia Cells through Reversal SHP-1 and SOCS-3 Hypermethylation: In Vitro and In Silico Evaluation

et al. 2021

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Epigenetic silencing of tumor suppressor genes (TSGs) plays an essential role in cancer pathogenesis, including acute myeloid leukemia (AML). All of SHP-1, SOCS-1, and SOCS-3 are TSGs that negatively regulate JAK/STAT signaling. Enhanced re-expression of TSGs through de-methylation represents a therapeutic target in several cancers. Thymoquinone (TQ) is a major component of Nigella sativa seeds with anticancer effects against several cancers. However, the effects of TQ on DNA methylation are not entirely understood. This study aimed to evaluate the ability of TQ to re-express SHP-1, SOCS-1, and SOCS-3 in MV4-11 AML cells through de-methylation. Cytotoxicity, apoptosis, and cell cycle assays were performed using WSTs-8 kit, Annexin V-FITC/PI apoptosis detection kit, and fluorometric-red cell cycle assay kit, respectively. The methylation of SHP-1, SOCS-1, and SOCS-3 was evaluated by pyrosequencing analysis. The expression of SHP-1, SOCS-1, SOCS-3, JAK2, STAT3, STAT5A, STAT5B, FLT3-ITD, DNMT1, DNMT3A, DNMT3B, TET2, and WT1 was assessed by RT-qPCR. The molecular docking of TQ to JAK2, STAT 3, and STAT5 was evaluated. The results revealed that TQ significantly inhibited the growth of MV4-11 cells and induced apoptosis in a dose- and time-dependent manner. Interestingly, the results showed that TQ binds the active pocket of JAK2, STAT3, and STAT5 to inhibit their enzymatic activity and significantly enhances the re-expression of SHP-1 and SOCS-3 through de-methylation. In conclusion, TQ curbs MV4-11 cells by inhibiting the enzymatic activity of JAK/STAT signaling through hypomethylation and re-expression of JAK/STAT negative regulators and could be a promising therapeutic candidate for AML patients.

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“…It is reported that phagosome pathway is the most optimal and common in both Kasumi-1 and MV4-11 AML cell lines induced by differentiation inducers, Trichostatin A and 5-Azacytidine ( Asmaa et al, 2020 ). Moreover, the phagosome pathway is involved in the MHC II and antigen processing and presentation (KEGG map 1 ).…”

Section: Discussionmentioning

confidence: 99%

OGP46 Induces Differentiation of Acute Myeloid Leukemia Cells via Different Optimal Signaling Pathways

Zhao

Wang

et al. 2021

Front. Cell Dev. Biol.

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Acute myelogenous leukemia (AML) is characterized by blockage of cell differentiation leading to the accumulation of immature cells, which is the most prevalent form of acute leukemia in adults. It is well known that all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) are the preferred drugs for acute promyelocytic leukemia (APL). However, they can lead to irreversible resistance which may be responsible for clinical failure after complete remission (CR). Moreover, the differentiation therapy of ATRA-based treatment has not been effective against AML with t(8;21) translocation. Here we aimed to identify the differentiation effect of OGP46 on AML cell lines (HL-60, NB4, and Kasumi-1) and explore its possible mechanisms. We found that OGP46 has significant inhibitory activity against these cells by triggering cell differentiation with cell-cycle exit at G1/G0 and inhibited the colony-formation capacity of the AML cells. It was shown that OGP46 induced the differentiation of NB4 cells via the transcriptional misregulation in cancer signaling pathway by PML-RARα depletion, while it was attributed to the hematopoietic cell lineage and phagosome pathway in Kasumi-1 cells, which are all critical pathways in cell differentiation. These results highlight that OGP46 is an active agent not only in the APL cell line NB4 but also in AML-M2 cell lines, especially Kasumi-1 with t(8;21) translocation. Therefore, OGP46 may be a potential compound for surmounting the differentiation blockage in AML.

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Transcriptomic Profiles of MV4-11 and Kasumi 1 Acute Myeloid Leukemia Cell Lines Modulated by Epigenetic Modifiers Trichostatin A and 5-Azacytidine

Cited by 5 publications

References 48 publications

Jiyuan Oridonin A Overcomes Differentiation Blockade in Acute Myeloid Leukemia Cells With MLL Rearrangements via Multiple Signaling Pathways

Jiyuan Oridonin A Overcomes Differentiation Blockade in Acute Myeloid Leukemia Cells With MLL Rearrangements via Multiple Signaling Pathways

Thymoquinone Inhibits Growth of Acute Myeloid Leukemia Cells through Reversal SHP-1 and SOCS-3 Hypermethylation: In Vitro and In Silico Evaluation

OGP46 Induces Differentiation of Acute Myeloid Leukemia Cells via Different Optimal Signaling Pathways

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