Low dosage of arsenic trioxide (As2O3) inhibits angiogenesis in epithelial ovarian cancer without cell apoptosis

Luo, Dehong; Zhang, Xiaoyuan; Du, Renle; Gao, Wenjuan; Luo, Na; Zhao, Shuangtao; Li, Yang; Chen, Rui; Wang, Hui; Bao, Yonghua; Yang, Wancai; Liu, Daishun; Shen, Wenzhi

doi:10.1007/s00775-018-1595-z

Cited by 19 publications

(13 citation statements)

References 37 publications

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“…A value of P < 0.05 was used as the criterion for statistical significance. An asterisk indicates a significant difference with P < 0.05, two asterisks indicate a significant difference with P < 0.01, and three asterisks indicate a significant difference with P < 0.001 [8,28].…”

Section: Discussionmentioning

confidence: 99%

Aspirin mediates histone methylation that inhibits inflammation-related stemness gene expression to diminish cancer stemness via COX-independent manner

Zhang

Luo

et al. 2020

Stem Cell Res Ther

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Background: The widely recognized anti-cancer potential of aspirin has created a broad interest to explore the clinical benefits of aspirin in cancer therapy. However, the current understanding of the molecular mechanisms involved in the anti-cancer potential of aspirin remains limited. Methods: Cancer stemness assays which contained ALDH, side population, chemo-resistance, sphere formation, and tumorigenesis were performed to validate aspirin function in vitro and in vivo. Histone modification assay was performed to check the effect of aspirin on histone methylation as well as the activity of HDAC and KDM6A/B. Inhibitor in vivo assay was performed to evaluate therapeutic effects of various inhibitor combination manners. Results: In regards to in vitro studies, aspirin diminishes cancer cell stemness properties which include reducing the ALDH+ subpopulation, side population, chemo-resistance, and sphere formation in three cancer types. In regards to in vivo studies, aspirin decreases tumor growth and metastasis and prolongs survival. In addition, our results showed that aspirin inhibits inflammation-related stemness gene expression (especially ICAM3) identified by a highthroughput siRNA platform. In regards to the underlying molecular mechanism of action, aspirin reduces histone demethylase (KDM6A/B) expression that mediates histone methylation and suppresses gene expression via a COXindependent manner. In regards to therapeutic strategies, aspirin combined HDM inhibitors, ICAM3 downstream signaling Src/PI3K inhibitors, or ICAM3 inhibitor Lifitigrast prevents cancer progression in vivo. Conclusions: The aforementioned findings suggest a molecular model that explains how aspirin diminishes cancer cell stemness properties. These findings may provide novel targets for therapeutic strategies involving aspirin in the prevention of cancer progression.

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Section: Discussionmentioning

confidence: 99%

Aspirin mediates histone methylation that inhibits inflammation-related stemness gene expression to diminish cancer stemness via COX-independent manner

Zhang

Luo

et al. 2020

Stem Cell Res Ther

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“…Cell lysates from different cell lines were prepared with RIPA buffer in the presence of protease inhibitor cocktails and Phosphatase Inhibitor Cocktail 2 and 3 (P8340, P5726, and P0044, Sigma-Aldrich, St Louis, MO, USA). Primary antibodies included the following: anti-Ki67 (Abcam Biotechnology, Inc., Abcam, Hong Kong), anti-P21, anti-caspase3, anti-P53, anti-p-JNK, anti-JNK, anti-p-P38, anti-P38, anti-p-ERK, anti-P38, and anti-β-actin (Santa Cruz Biotechnology Inc, Santa Cruz, CA, USA), and anti-PPA1 (Sigma-Aldrich St Louis, MO, USA) 34 .…”

Section: Methodsmentioning

confidence: 99%

PPA1 promotes NSCLC progression via a JNK- and TP53-dependent manner

et al. 2019

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Inorganic pyrophosphatase (PPA1) promotes tumor progression in several tumor types. However, the underlying mechanism remains elusive. Here, we disclosed that PPA1 expression is markedly upregulated in lung carcinoma tissue versus normal lung tissue. We also found that the non-small cell lung cancer (NSCLC) cell lines show increased PPA1 expression levels versus normal lung cell line control. Moreover, the knockdown of PPA1 promotes cell apoptosis and inhibits cell proliferation. Whereas, the ectopic expression of PPA1 reduces cell apoptosis and enhances cell proliferation. Most interestingly, the expression of mutant PPA1 (D117A) significantly abolishes PPA1-mediated effect on cell apoptosis and proliferation. The underlying mechanism demonstrated that TP53 expression deficiency or JNK inhibitor treatment could abolish PPA1-mediated NSCLC progression. In summary, the aforementioned findings in this study suggest a new pathway the PPA1 mediates NSCLC progression either via TP53 or JNK. Most important, the pyrophosphatase activity is indispensible for PPA1-mediated NSCLC progression. This may provide a promising target for NSCLC therapy.

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“…Combined treatment with retinoic acid (RA) and ATO has been demonstrated to be curative for the majority of patients with APL (7–9). Furthermore, an increasing number of studies have proven the anti-carcinogenic properties of ATO in different tumors, including in gastric cancer (10), lymphoma (11), bladder cancer (12), head and neck cancer (13), and ovarian cancer (14). Although it has been reported that ATO may inhibit the progression of pancreatic cancer (15), the potential targets and molecular mechanisms of action of ATO remain unclear.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the target genes of arsenic trioxide in pancreatic cancer by bioinformatics analysis

et al. 2019

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The aim of the present study was to evaluate the potential network of arsenic trioxide (ATO) target genes in pancreatic cancer. The DrugBank, STITCH, cBioPortal, Kaplan-Meier plotter and Oncomine websites were used to analyze the association of ATO and its target genes with pancreatic cancer. Initially, 19 ATO target genes were identified, along with their associated protein-protein interaction networks and Kyoto Encyclopedia of Genes and Genomes pathways. ATO was found to be associated with multiple types of cancer, and the most common solid cancer was pancreatic cancer. A total of 6 ATO target genes (namely AKT1, CCND1, CDKN2A, IKBKB, MAPK1 and MAPK3) were found to be associated with pancreatic cancer. Next, the mutation information of the 6 ATO target genes in pancreatic cancer was collected. A total of 20 ATO interacting genes were identified, which were mainly involved in hepatitis B, prostate cancer, pathways in cancer, glioma and chronic myeloid leukemia. Finally, the genes CCND1 and MAPK1 were detected to be prognostic factors in patients with pancreatic cancer. In conclusion, bioinformatics analysis may help elucidate the molecular mechanisms underlying the involvement of ATO in pancreatic cancer, enabling more effective treatment of this disease.

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Low dosage of arsenic trioxide (As2O3) inhibits angiogenesis in epithelial ovarian cancer without cell apoptosis

Cited by 19 publications

References 37 publications

Aspirin mediates histone methylation that inhibits inflammation-related stemness gene expression to diminish cancer stemness via COX-independent manner

Aspirin mediates histone methylation that inhibits inflammation-related stemness gene expression to diminish cancer stemness via COX-independent manner

PPA1 promotes NSCLC progression via a JNK- and TP53-dependent manner

Evaluation of the target genes of arsenic trioxide in pancreatic cancer by bioinformatics analysis

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