Arsenic trioxide inhibits the proliferation of myeloma cell line through notch signaling pathway

Hu, Jian; Xiao, Heng; Hong, Xiuli; Lu, Quanyi; Zhu, Xiaoyan

doi:10.1186/1475-2867-13-25

Cited by 15 publications

(12 citation statements)

References 27 publications

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“…In preclinical studies, ATO stimulates differentiation (through degradation the PML‐RARΑ fusion protein) (Chen et al , ), as well as activation of cell death pathways by intrinsic (Morales et al , ) or extrinsic apoptosis (Liu et al , ) and autophagy (Lau et al , ). Moreover, ATO activates signal transduction proteins (JNK and p38) (Wen et al , ), downregulates extracellular surface molecules (Notch receptor and the Notch ligand JAG2) (Hu et al , ), and upregulates defence mechanisms [reactive oxygen species (ROS) and glutathione (GSH) level] (Matulis et al , ). Our data showed that NREA treatment in MM triggered more pronounced activation of JNK than ATO, followed by degradation of total JNK protein.…”

Section: Discussionmentioning

confidence: 99%

Realgar nanoparticles versus ATO arsenic compounds induce in vitro and in vivo activity against multiple myeloma

et al. 2017

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Summary Multiple myeloma (MM), a B cell malignancy characterized by clonal proliferation of plasma cells in the bone marrow, remains incurable despite the use of novel and conventional therapies. In this study, we demonstrated MM cell cytotoxicity triggered by realgar (REA; As4S4) nanoparticles (NREA) versus Arsenic trioxide (ATO) against MM cell lines and patient cells. Both NREA and ATO showed in vivo anti-MM activity, resulting in significantly decreased tumour burden. The anti-MM activity of NREA and ATO is associated with apoptosis, evidenced by DNA fragmentation, depletion of mitochondrial membrane potential, cleavage of caspases and anti-apoptotic proteins. NREA induced G2/M cell cycle arrest and modulation of cyclin B1, p53 (TP53), p21 (CDNK1A), Puma (BBC3) and Wee-1 (WEE1). Moreover, NREA induced modulation of key regulatory molecules in MM pathogenesis including JNK activation, c-Myc (MYC), BRD4, and histones. Importantly, NREA, but not ATO, significantly depleted the proportion and clonogenicity of the MM stem-like side population, even in the context of the bone marrow stromal cells. Finally, our study showed that both NREA and ATO triggered synergistic anti-MM activity when combined with lenalidomide or melphalan. Taken together, the anti-MM activity of NREA was more potent compared to ATO, providing the preclinical framework for clinical trials to improve patient outcome in MM.

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Section: Discussionmentioning

confidence: 99%

Realgar nanoparticles versus ATO arsenic compounds induce in vitro and in vivo activity against multiple myeloma

et al. 2017

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“…ATO has been reported to inhibit Notch pathway in several human cancers. [41][42][43] For example, ATO depleted the cancer stem-like cell population in gliomas via inhibition of Notch pathway. 41,43 Similarly, ATO inhibited repopulation of neurosphere derived from glioblastoma by down-regulation of Notch pathway.…”

Section: Discussionmentioning

confidence: 99%

“…44 Hu et al found that ATO inhibited the proliferation of myeloma cell line through suppression of Notch signaling pathway. 42 Yang et al reported that ATO exerted antilung cancer activity via inhibition of Notch-1. 45 In line with these findings, we observed that ATO down-regulated Notch-1 expression in breast cancer cells.…”

Section: Discussionmentioning

confidence: 99%

Arsenic trioxide inhibits cell growth and motility via up-regulation of let-7a in breast cancer cells

et al. 2017

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Arsenic trioxide (ATO) has been reported to exert its anti-cancer activities in human cancers. However, the molecular mechanism of ATO-triggered anti-tumor activity has not been fully elucidated. Recently, multiple studies demonstrated that ATO could regulate miRNAs in human cancers. Therefore, in this study, we investigated whether ATO regulated let-7a in breast cancer cells. We found that ATO upregulated let-7a level in breast cancer cells. We also found that up-regulation of let-7a inhibited cell growth and induced apoptosis and retarded cell migration and invasion. We also observed that up-regulation of let-7a enhanced cell growth inhibition and invasion suppression induced by ATO treatment. Our findings suggest that ATO suppressed cell growth, stimulated apoptosis, and retarded cell invasion partly via upregulation of let-7a in breast cancer cells. Our study provides a new anti-tumor mechanism of ATO treatment in breast cancer.

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“…As 2 O 3 is a safe, effective treatment for patients with acute promyelocytic leukemia, and it has also shown promising results in patients with relapsed multiple myeloma. 30 In addition, a wide range of malignancies, including hematologic cancer and solid tumors derived from several tissue types, are susceptible to As 2 O 3 treatment. 31 Here, we found that As 2 O 3 inhibited the viability ( Figure 1 ) and induced apoptosis ( Figure 2 ) of LNCaP and PC3 cells in a dose-dependent manner.…”

Section: Discussionmentioning

confidence: 99%

Arsenic trioxide inhibits viability and induces apoptosis through reactivating the Wnt inhibitor secreted frizzled related protein-1 in prostate cancer cells

Zheng¹,

Jiang²,

Zhang³

et al. 2016

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BackgroundGrowing evidence suggests that arsenic trioxide (As2O3) induces apoptosis and inhibits tumor cell growth in prostate cancer (PCa), although details of the mechanism are still inconclusive. We investigated the antitumor effect of As2O3 in human PCa cell lines LNCaP and PC3 and the underlying mechanisms by focusing on the Wnt signaling pathway.MethodsThe effect of As2O3 on the viability and apoptosis of PCa cells was investigated by cholecystokinin-8 and flow cytometry. The expression of the related proteins in the Wnt signaling pathway and the downstream target genes of the Wnt signaling pathway was examined by Western blot and quantitative real-time PCR assay. The methylation status of the SFRP1 gene promoter was assessed by bisulfite sequencing.ResultsAs2O3 inhibited the viability of PCa cells and induced apoptosis of PCa cells in a dose-dependent manner. The protein level of phosphoglycogen synthase kinase-3β was upregulated, whereas the protein level of β-catenin and the mRNA levels of c-MYC, MMP-7, and COX-2 were downregulated in a dose-dependent manner in PCa cells treated with As2O3. In addition, As2O3 upregulated the protein and mRNA levels of secreted frizzled related protein-1, and increased the demethylation of the SFRP1 gene promoter.ConclusionOur results suggest that As2O3 may inhibit cell viability and induce apoptosis through reactivating the Wnt inhibitor secreted frizzled related protein-1 in both androgen-dependent and -independent human PCa.

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Arsenic trioxide inhibits the proliferation of myeloma cell line through notch signaling pathway

Cited by 15 publications

References 27 publications

Realgar nanoparticles versus ATO arsenic compounds induce in vitro and in vivo activity against multiple myeloma

Realgar nanoparticles versus ATO arsenic compounds induce in vitro and in vivo activity against multiple myeloma

Arsenic trioxide inhibits cell growth and motility via up-regulation of let-7a in breast cancer cells

Arsenic trioxide inhibits viability and induces apoptosis through reactivating the Wnt inhibitor secreted frizzled related protein-1 in prostate cancer cells

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