Dioscin induces demethylation of DAPK-1 and RASSF-1alpha genes via the antioxidant capacity, resulting in apoptosis of bladder cancer T24 cells

Zhou, Qiang; Song, Wie; Xiao, Wei

doi:10.17179/excli2016-571

Cited by 9 publications

(1 citation statement)

References 19 publications

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“…The loss of DAPK-1 expression in cancer cell lines has been demonstrated to be due to epigenetic silencing via DNA hypermethylation [ 62 ]. Numerous malignancies have been linked with DAPK-1 hypermethylation and loss of its expression, and these include bladder [ 78 ], kidney [ 79 ], gastric [ 80 ], head and neck [ 81 ], thyroid [ 82 ], lung [ 31 ], ovarian [ 83 ] and cervical cancers [ 71 , 72 , 76 ]. Apoptosis is one of the processes that are affected by DAPK-1 silencing, thus leading to cancer development and progression.…”

Section: Cellular Functions Of Dapk-1mentioning

confidence: 99%

The Role of Death-Associated Protein Kinase-1 in Cell Homeostasis-Related Processes

Makgoo

Mosebi

Mbita

2023

Genes

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Tremendous amount of financial resources and manpower have been invested to understand the function of numerous genes that are deregulated during the carcinogenesis process, which can be targeted for anticancer therapeutic interventions. Death-associated protein kinase 1 (DAPK-1) is one of the genes that have shown potential as biomarkers for cancer treatment. It is a member of the kinase family, which also includes Death-associated protein kinase 2 (DAPK-2), Death-associated protein kinase 3 (DAPK-3), Death-associated protein kinase-related apoptosis-inducing kinase 1 (DRAK-1) and Death-associated protein kinase-related apoptosis-inducing kinase 2 (DRAK-2). DAPK-1 is a tumour-suppressor gene that is hypermethylated in most human cancers. Additionally, DAPK-1 regulates a number of cellular processes, including apoptosis, autophagy and the cell cycle. The molecular basis by which DAPK-1 induces these cell homeostasis-related processes for cancer prevention is less understood; hence, they need to be investigated. The purpose of this review is to discuss the current understanding of the mechanisms of DAPK-1 in cell homeostasis-related processes, especially apoptosis, autophagy and the cell cycle. It also explores how the expression of DAPK-1 affects carcinogenesis. Since deregulation of DAPK-1 is implicated in the pathogenesis of cancer, altering DAPK-1 expression or activity may be a promising therapeutic strategy against cancer.

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Section: Cellular Functions Of Dapk-1mentioning

confidence: 99%

The Role of Death-Associated Protein Kinase-1 in Cell Homeostasis-Related Processes

Makgoo

Mosebi

Mbita

2023

Genes

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An integrated approach to elucidate signaling pathways of dioscin-induced apoptosis, energy metabolism and differentiation in acute myeloid leukemia

Chan

Liang

Guh

2018

Naunyn-Schmiedeberg's Arch Pharmacol

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Although the therapeutics have improved the rates of remission and cure of acute myelogenous leukemia (AML) in recent decades, there is still an unmet medical need for AML therapies because disease relapses are a major obstacle in patients who become refractory to salvage therapy. The development of therapeutic agents promoting both cytotoxicity and cell differentiation may provide opportunities to improve the clinical outcome. Dioscin-induced apoptosis in leukemic cells was identified through death receptor-mediated extrinsic apoptosis pathway. The formation of Bak and tBid, and loss of mitochondrial membrane potential were induced by dioscin suggesting the activation of intrinsic apoptotsis pathway. A functional analysis of transcription factors using transcription factor-DNA interaction array and IPA analysis demonstrated that dioscin induced a profound increase of protein expression of CCAAT/enhancer-binding protein α (C/EBPα), a critical factor for myeloid differentiation. Two-dimensional gel electrophoresis assay confirmed the increase of C/EBPα expression. Dioscin-induced differentiation was substantiated by an increase of CD11b protein expression and the induction of differentiation toward myelomonocytic/granulocytic lineages using hematoxylin and eosin staining. Moreover, both glycolysis and gluconeogenesis pathways after two-dimensional gel electrophoresis assay and IPA network enrichment analysis were proposed to dioscin action. In conclusion, the data suggest that dioscin exerts its antileukemic effect through the upregulation of both death ligands and death receptors and a crosstalk activation of mitochondrial apoptosis pathway with the collaboration of tBid and Bak formation. In addition, proteomics approach reveals an altered metabolic signature of dioscin-treated cells and the induction of differentiation of promyelocytes to granulocytes and monocytes in which the C/EBPα plays a key role.

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Targeting Major Signaling Pathways of Bladder Cancer with Phytochemicals: A Review

Chestnut

Subramaniam

Dandawate

et al. 2020

Nutrition and Cancer

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Dioscin induces demethylation of DAPK-1 and RASSF-1alpha genes via the antioxidant capacity, resulting in apoptosis of bladder cancer T24 cells

Cited by 9 publications

References 19 publications

The Role of Death-Associated Protein Kinase-1 in Cell Homeostasis-Related Processes

The Role of Death-Associated Protein Kinase-1 in Cell Homeostasis-Related Processes

An integrated approach to elucidate signaling pathways of dioscin-induced apoptosis, energy metabolism and differentiation in acute myeloid leukemia

Targeting Major Signaling Pathways of Bladder Cancer with Phytochemicals: A Review

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