Effects of JS-K, a novel anti-cancer nitric oxide prodrug, on gene expression in human hepatoma Hep3B cells

Dong, Ray; Wang, Xueqian; Wang, Huan; Liu, Zhengyun; Liu, Jie; Saavedra, Joseph E.

doi:10.1016/j.biopha.2017.01.080

Cited by 18 publications

(16 citation statements)

References 32 publications

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“…This finding is consistent with a recent report that luteolin, a common dietary flavonoid, induces the ER stress response and mitochondrial dysfunction by increasing intracellular ROS levels in glioblastoma cells [40]. Another study reported that JS-K, a glutathione S transferase (GST)-activated nitric oxide (NO) donor prodrug, promotes apoptosis by inducing ROS production in human prostate cancer cells [41]. It was shown that arsenic sulfide induces apoptosis and autophagy through the accumulation of ROS in osteosarcoma cells [42].…”

Section: Discussionsupporting

confidence: 82%

Protodioscin Induces Apoptosis Through ROS-Mediated Endoplasmic Reticulum Stress via the JNK/p38 Activation Pathways in Human Cervical Cancer Cells

Lin

Lee

Chen

et al. 2018

Cell Physiol Biochem

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Background/Aims: Protodioscin (PD) is a steroidal saponin with anti-cancer effects on a number of cancer cells, but the anti-tumor effects and mechanism of action of PD on human cervical cancer cells is unclear. Methods: We determined cell viability using the MTT assay. Cell death, mitochondrial membrane potential (MMP), intracellular reactive oxygen species (ROS) generation, and endoplasmic reticulum (ER) stress were measured on a flow cytometry. Caspase activation, ER stress, and MMP-dependent apoptosis proteins in cervical cancer cells in response to PD were determined by Western blot analysis. The ability of ATF4 binding to ChIP promoter was measured using the ChIP assay. Results: We demonstrated that PD inhibits cell viability, causes a loss of mitochondrial function, and induces apoptosis, as evidenced by up-regulation of caspase-8, -3, -9, -PARP, and Bax activation, and down-regulation of Bcl-2 expression. PD was shown to induce ROS and the ER stress pathway, including GRP78, p-eIF-2α, ATF4, and CHOP. Pre-treatment with NAC, a ROS production inhibitor, significantly reduced ER stress and apoptosis-related proteins induced by PD. Transfection of GRP78/CHOP-siRNA effectively inhibited PD-induced ER stress-dependent apoptosis. Moreover, treatment with PD significantly increased p38 and JNK activation. Co-administration of a JNK inhibitor (SP600125) or p38 inhibitor (SB203580) abolished cell death and ER stress effects during PD treatment. In addition, PD induced the expression of nuclear ATF4 and CHOP, as well as the binding ability of ATF4 to the CHOP promoter. Conclusion: Our results suggest that PD is a promising therapeutic agent for the treatment of human cervical cancer.

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Section: Discussionsupporting

confidence: 82%

Protodioscin Induces Apoptosis Through ROS-Mediated Endoplasmic Reticulum Stress via the JNK/p38 Activation Pathways in Human Cervical Cancer Cells

Lin

Lee

Chen

et al. 2018

Cell Physiol Biochem

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“…Based on this information, cell viability and colony formation assays were used in this research to emphasize the impact of the RSNO, GSNO on N2a neuroblastoma cells. Similar to previous studies [25][26][27][28][29]32,33], direct and indirect effects of NO were analyzed collectively (not distinguished) in this work. These experiments showed that after 24 h of exposure to GSNO, 21-24% of cells were no longer metabolically active and 100% were incapable of colony formation.…”

Section: Discussionmentioning

confidence: 92%

“…Although NO concentration can be directly manipulated, it is more challenging to control release kinetics and site-specific delivery of NO. To address these challenges various delivery platforms have been explored [23][24][25][26][27][28][29][30][31].…”

Section: Discussionmentioning

confidence: 99%

“…Various NO-based therapeutics have been utilized in cancer research, including nitrated fatty acids, NO-loaded nanoparticles, and NO-donors [25][26][27][28][29][32][33][34][35][36]40]. NO-donors including diazeniumdiolates and RSNOs have been successfully applied to influence or control NO release kinetics in anticancer research [25][26][27][28][29]32,33,40]. Diazeniumdiolates, which consist of two moles of NO per molecule (vs one mole of NO per RSNO molecule), result in higher concentrations of NO-release than RSNOs.…”

Section: Discussionmentioning

confidence: 99%

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Nitric Oxide as a Potential Adjuvant Therapeutic for Neuroblastoma: Effects of NO on Murine N2a Cells

Gordon

Reynolds

Brown

2020

Veterinary Sciences

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Neuroblastoma, the most common extracranial solid tumor in children, accounts for 15% of all pediatric cancer deaths. Pharmaceutical applications of S-Nitrosylation, which, under normal conditions is involved with a host of epigenetic and embryological development pathways, have exhibited great potential for use as adjuvant therapeutics in the clinical management of cancer. Herein, an evaluation of the impact of nitric oxide (NO) as a potent anticancer agent on murine neuroblastoma cells is presented. Excitingly cell viability, colony formation, and non-carcinogenic cell analysis illustrate the significance and practicality of NO as a cytotoxic anticancer therapeutic. Resazurin, WST-8 (2-(2-methoxy-4-nitrophenyl)-3-(4-nitrophenyl)-5-(2,4-disulfophenyl)-2H-tetrazolium, monosodium salt), and MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-diphyltetrazolium bromide) assays consistently displayed a moderate,~20-25% reduction in cell viability after exposure to 1 mM S-Nitrosoglutathione (GSNO). A colony formation assay demonstrated that treated cells no longer exhibited colony formation capacity. Identically GSNO-treated Adult Human Dermal Fibroblasts (HDFa) exhibited no decrease in viability, indicating potential discrimination between neoplastic and normal cells. Collectively, our findings indicate a potential application for NO as an adjuvant therapeutic in the clinical management of neuroblastoma. Vet. Sci. 2020, 7, 51 2 of 15 and intricacy of disease progression and response to treatment, the International Neuroblastoma Staging System (INSS) was developed to classify the extent of the disease and impact the treatment approach [13]. Three distinct stages comprise the INSS: low, intermediate, and high risk. Each risk group is comprised of definitions containing the stage(s), patient age, presence/absence of the MYCN gene, histology, and DNA ploidy. Currently, low risk tumors represent ≤25% of initial diagnoses, intermediate risk represent about~15% of initial diagnoses, and high risk tumors are the most commonly diagnosed, at ≥60% [11]. In patients with low risk disease, surgery and observation are the central therapeutic options that contribute to >90% survival [14,15]. Patients with intermediate risk disease typically receive a variety of sequential treatments including chemotherapy, surgery, and radiation therapy, if necessary. Survival rates in this group drop some but remain favorable at >80% [16,17]. High risk treatment protocols commence in an identical manner and additional treatments are frequently required, such as immunotherapy and bone marrow transplant. Despite the advances in treatments for low and intermediate risk disease, patients with high risk disease continue to face particularly poor prognosis, with~40% five-year overall survival rates [18,19]. Overall relapse rates are additionally overwhelming, at >60% [12]. In a similar fashion, treatments for recurrent low-risk and intermediate-risk disease are largely effective. However, recurrent high-risk neuroblastoma remains a significant challenge. Due to the a...

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“…Endothelial progenitor cells exposed to laminar flow, a known activator of eNOS, upregulated NO concurrent with downregulation of TSP1 protein (7). In contrast to these results in primary vascular and renal cells, treatment of human hepatoma3 B cancer cells with the NO prodrug O2-(2,4-dinitrophenyl) 1-[(4-ethoxyxarbonyl)piperazin-1-yl] diazen-1-ium 1,2-diolate (1 to 10 lM) increased TSP1 mRNA expression and cell surface expression of the TSP1 receptor CD36 (44). Conversely, treatment of NIH 3T3 cells with high concentrations of NO (1 mM DETA/NO) for 24 h suppressed TSP2 promoter activity and mRNA (149).…”

Section: E No Regulation Of Tsp1 Expressionmentioning

confidence: 65%

Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer

Roberts

Kaur

Isenberg

2017

Antioxidants & Redox Signaling

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Significance: In contrast to structural elements of the extracellular matrix, matricellular proteins appear transiently during development and injury responses, but their sustained expression can contribute to chronic disease. Through interactions with other matrix components and specific cell surface receptors, matricellular proteins regulate multiple signaling pathways, including those mediated by reactive oxygen and nitrogen species and H 2 S. Dysregulation of matricellular proteins contributes to the pathogenesis of vascular diseases and cancer. Defining the molecular mechanisms and receptors involved is revealing new therapeutic opportunities. Recent Advances: Thrombospondin-1 (TSP1) regulates NO, H 2 S, and superoxide production and signaling in several cell types. The TSP1 receptor CD47 plays a central role in inhibition of NO signaling, but other TSP1 receptors also modulate redox signaling. The matricellular protein CCN1 engages some of the same receptors to regulate redox signaling, and ADAMTS1 regulates NO signaling in Marfan syndrome. In addition to mediating matricellular protein signaling, redox signaling is emerging as an important pathway that controls the expression of several matricellular proteins. Critical Issues: Redox signaling remains unexplored for many matricellular proteins. Their interactions with multiple cellular receptors remains an obstacle to defining signaling mechanisms, but improved transgenic models could overcome this barrier. Future Directions: Therapeutics targeting the TSP1 receptor CD47 may have beneficial effects for treating cardiovascular disease and cancer and have recently entered clinical trials. Biomarkers are needed to assess their effects on redox signaling in patients and to evaluate how these contribute to their therapeutic efficacy and potential side effects. Antioxid. Redox Signal. 27, 874-911.

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Effects of JS-K, a novel anti-cancer nitric oxide prodrug, on gene expression in human hepatoma Hep3B cells

Cited by 18 publications

References 32 publications

Protodioscin Induces Apoptosis Through ROS-Mediated Endoplasmic Reticulum Stress via the JNK/p38 Activation Pathways in Human Cervical Cancer Cells

Protodioscin Induces Apoptosis Through ROS-Mediated Endoplasmic Reticulum Stress via the JNK/p38 Activation Pathways in Human Cervical Cancer Cells

Nitric Oxide as a Potential Adjuvant Therapeutic for Neuroblastoma: Effects of NO on Murine N2a Cells

Regulation of Cellular Redox Signaling by Matricellular Proteins in Vascular Biology, Immunology, and Cancer

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