Staurosporine Induced Apoptosis Rapidly Downregulates TDP-43 in Glioma Cells

Nan, Yi-Nan; Zhu, Jianming; Tan, Yan; Zhang, Qi; Jia, William; Hua, Qian

doi:10.7314/apjcp.2014.15.8.3575

Cited by 14 publications

(12 citation statements)

References 33 publications

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“…Although caspase 3/7 is not essential for methuotic cell death [8, 22], we found that caspase 3/7 activation as well as endogenous caspase 3/7 activity is counter regulated by exogenous ATP (Figure 2). In the glioma cell line #12537-GB, Vac-induced caspase 3/7 activation and STS-induced apoptosis occur within a similar time frame (Figures 2, 3, [32, 33]). However, the number of PI-positive nuclei in STS- and Vac-treated glioma cells differed between Vac- and STS-induced cell death (Figure 3A).…”

Section: Discussionmentioning

confidence: 87%

Vacquinol-1 inducible cell death in glioblastoma multiforme is counter regulated by TRPM7 activity induced by exogenous ATP

et al. 2017

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Glioblastomas (GBM) are the most malignant brain tumors in humans and have a very poor prognosis. New therapeutic options are urgently needed. A novel drug, Vacquinol-1 (Vac), a quinolone derivative, displays promising properties by inducing rapid cell death in GBM but not in non-transformed tissues. Features of this type of cell death are compatible with a process termed methuosis. Here we tested Vac on a highly malignant glioma cell line observed by long-term video microscopy. Human dental-pulp stem cells (DPSCs) served as controls. A major finding was that an exogenous ATP concentration of as little as 1 μM counter regulated the Vac-induced cell death. Studies using carvacrol, an inhibitor of transient receptor potential cation channel, subfamily M, member 7 (TRPM7), demonstrated that the ATP-inducible inhibitory effect is likely to be via TRPM7. Exogenous ATP is of relevance in GBM with large necrotic areas. Our results support the use of GBM cultures with different grades of malignancy to address their sensitivity to methuosis. The video-microscopy approach presented here allows decoding of signaling pathways as well as mechanisms of chemotherapeutic resistance by long-term observation. Before implementing Vac as a novel therapeutic drug in GBM, cells from each individual patient need to be assessed for their ATP sensitivity. In summary, the current investigation supports the concept of methuosis, described as non-apoptotic cell death and a promising approach for GBM treatment. Tissue-resident ATP/necrosis may interfere with this cell-death pathway but can be overcome by a natural compound, carvacrol that even penetrates the blood-brain barrier.

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Section: Discussionmentioning

confidence: 87%

Vacquinol-1 inducible cell death in glioblastoma multiforme is counter regulated by TRPM7 activity induced by exogenous ATP

et al. 2017

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“…These results imply that TDP43 could be a drug target in breast cancer, especially in TNBC. Interestingly, it has been reported that many antitumor drugs can alter TDP43 expression in cancer cells ( 44 – 46 ), further suggesting that TDP43 might provide a molecular basis for the treatment of breast cancer.…”

Section: Discussionmentioning

confidence: 99%

Loss of TDP43 inhibits progression of triple-negative breast cancer in coordination with SRSF3

Hao

Zhao

Zhang

et al. 2018

Proc. Natl. Acad. Sci. U.S.A.

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SignificanceTriple-negative breast cancer (TNBC) is responsible for significant mortality among breast cancer subtypes, with its treatment largely unsuccessful due to ineffective targeted therapies. Our bioinformatics analysis demonstrates a unique alternative splicing pattern in TNBC compared with those of other breast cancers. In analyzing the underlying mechanism of the distinct alternative splicing profile, TDP43, a critical gene previously implicated in neurodegenerative disease, is found to promote TNBC progression. Mechanistically, TDP43 regulates extensive alternative splicing events, including downstream gene PAR3, by forming a complex with SRSF3 to regulate alternative splicing events coordinately. Splicing factors TDP43 and SRSF3, which are likely responsible for the unique alternative splicing, could serve as potential targets for TNBC therapy.

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“…Knockdown of TDP-43 by a specific siRNA dramatically enhances the cytotoxicity of STS, suggesting that normal levels of TDP-43 are protective for cancer cells under apoptotic insult (Nan et al 2014). This observation is consistent with previous analysis showing TDP-43 as survival factor under oxidative stress conditions (Higashi et al 2013).…”

Section: Tdp-43mentioning

confidence: 99%

RNA-binding proteins as molecular links between cancer and neurodegeneration

et al. 2014

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For many years, epidemiological studies have suggested an association between cancer and neurodegenerative disorders-two disease processes that seemingly have little in common. Although these two disease processes share disruptions in a wide range of cellular pathways, including cell survival, cell death and the cell cycle, the end result is very divergent: uncontrolled cell survival and proliferation in cancer and progressive neuronal cell death in neurodegeneration. Despite the clinical data connecting these two disease processes, little is known about the molecular links between them. Among the mechanisms affected in cancer and neurodegenerative diseases, alterations in RNA metabolism are obtaining significant attention given the critical role for RNA transcription, maturation, transport, stability, degradation and translation in normal cellular function. RNA-binding proteins (RBPs) are integral to each stage of RNA metabolism through their participation in the formation of ribonucleoprotein complexes (RNPs). RBPs have a broad range of functions including posttranscriptional regulation of mRNA stability, splicing, editing and translation, mRNA export and localization, mRNA polyadenylation and miRNA biogenesis, ultimately impacting the expression of every single gene in the cell. In this review, we examine the evidence for RBPs as being key a molecular linkages between cancer and neurodegeneration.

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Staurosporine Induced Apoptosis Rapidly Downregulates TDP-43 in Glioma Cells

Cited by 14 publications

References 33 publications

Vacquinol-1 inducible cell death in glioblastoma multiforme is counter regulated by TRPM7 activity induced by exogenous ATP

Vacquinol-1 inducible cell death in glioblastoma multiforme is counter regulated by TRPM7 activity induced by exogenous ATP

Loss of TDP43 inhibits progression of triple-negative breast cancer in coordination with SRSF3

RNA-binding proteins as molecular links between cancer and neurodegeneration

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