The yin and yang of nitric oxide in cancer progression

Burke, Amy J.; Sullivan, Frank; Giles, Francis J.; Glynn, Sharon A.

doi:10.1093/carcin/bgt034

Cited by 318 publications

(310 citation statements)

References 137 publications

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“…Unfortunately, these assays only make an approximation of the NO level within a solution, a problem that has led researchers to find contradictory results when comparing the predicted NO levels through different analysis methods [60]. sulfanilamide in phosphoric acid and then N-1-napthylethylenediamine dihydrochloride to the samples of interest, as depicted in Figure 2 [59].…”

Section: Upstream and Downstream Measurementsmentioning

confidence: 99%

“…The Griess method uses standard biology-and chemistry-based methods in combination with instruments that are commercially available. Unfortunately, these assays only make an approximation of the NO level within a solution, a problem that has led researchers to find contradictory results when comparing the predicted NO levels through different analysis methods [60]. An alternate method of predicting NO concentration within a system is performed by examining upstream components such as NOS activity.…”

Section: Upstream and Downstream Measurementsmentioning

confidence: 99%

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Nitric Oxide Sensors for Biological Applications

2018

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Nitric oxide (NO) is an essential signaling molecule within biological systems and is believed to be involved in numerous diseases. As a result of NO's high reaction rate, the detection of the concentration of NO, let alone the presence or absence of the molecule, is extremely difficult. Researchers have developed multiple assays and probes in an attempt to quantify NO within biological solutions, each of which has advantages and disadvantages. This review highlights many of the current NO sensors, from those that are commercially available to the newest sensors being optimized in research labs, to assist in the understanding and utilization of NO sensors in biological fields.

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Section: Upstream and Downstream Measurementsmentioning

confidence: 99%

Section: Upstream and Downstream Measurementsmentioning

confidence: 99%

Nitric Oxide Sensors for Biological Applications

2018

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“…DDAH-2 functionsas an inhibitor of nitric oxide (NO) synthase. NO overexpression has been reported in various tumors, including lung cancer, and its inhibition is regarded as an anticancer therapy (28). Cancer cells are able to evade cell cycle arrest via VHR overexpression (29).…”

Section: Discussionmentioning

confidence: 99%

Immune-associated proteins with potential in vivo anti-tumor activities are upregulated in lung cancer cells treated with umbelliprenin: A proteomic approach

et al. 2016

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Abstract. Umbelliprenin (Umb), a natural coumarin, has demonstrated anti-tumor activities, both in vitro and particularly in vivo, in several types of cancer, including lung cancer. The present study aimed to identify molecular targets of Umb using a high-throughput approach. Lung cancer cell lines, QU-DB (large-cell lung carcinoma) and A549 (adenocarcinoma), were treated with Umb. Differentially-expressed proteins were identified using two-dimensional electrophoresis coupled to mass spectrometry. In the QU-DB cells, differential expression of proteins, including downregulation of the tumorigenic protein heat shock protein 90 kDa and upregulation of the potential anti-tumor proteins Nipsnap1 and glycine-tRNA ligase (GRS), suggested that Umb is a strong anti-tumor compound. In the A549 cells, differential expression of proteins indicated possible contradictory effects of Umbregarding tumorigenesis, which included downregulation of the tumorigenic protein cyclophilin and the tumor suppressor MST, and upregulation of stathmin (tumorigenic) and calreticulin. Calreticulun, in addition to GRS in QU-DB cells, stimulates anti-tumor immune responses in vivo. To the best of our knowledge, the present study is the first to use a high-throughput approach to identify targets of Umb in cancer. These molecular targets suggested that Umb may exhibit stronger in vitro anti-tumor activity against the large-cell carcinoma model than the adenocarcinoma model. Furthermore, it has been reported that Umb exhibits higher cytotoxicity against QU-DB cells than A549 cells in vitro, and significant Umb anti-tumor activity against lung cancer in vivo, which is consistent with previously published literature. In each cell type, immune-associated molecules were upregulated, indicating that this naturally occurring compound exhibits marked anti-tumor activity in vivo. However, further studies that investigate the effect of Umb in different in vitro models of cancer are required.

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“…57,58 Dichotomous effects of NO have been observed on important processes of cancer biology such as proliferation, apoptosis, migration, invasion, and angiogenesis. 59 Nevertheless, it has been shown that NO effects depend on the source and concentration of the gas in the tumor area, affecting the cancer and surrounding cells. 58 In cancer models, low levels of NO (,100 nM) generated by eNOS increase proliferation and angiogenesis, and higher levels of NO produced by iNOS (.500 nM) cause DNA damage, oxidative stress, cytotoxicity, and apoptosis of cancer cells.…”

Section: Drewes Et Almentioning

confidence: 99%

Novel therapeutic mechanisms determine the effectiveness of lipid-core nanocapsules on melanoma models

Drewes¹,

Fiel²,

Bexiga³

et al. 2016

IJN

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Melanoma is a severe metastatic skin cancer with poor prognosis and no effective treatment. Therefore, novel therapeutic approaches using nanotechnology have been proposed to improve therapeutic effectiveness. Lipid-core nanocapsules (LNCs), prepared with poly(ε-caprolactone), capric/caprylic triglyceride, and sorbitan monostearate and stabilized by polysorbate 80, are efficient as drug delivery systems. Here, we investigated the effects of acetyleugenol-loaded LNC (AcE-LNC) on human SK-Mel-28 melanoma cells and its therapeutic efficacies on melanoma induced by B16F10 in C57B6 mice. LNC and AcE-LNC had z -average diameters and zeta potential close to 210 nm and -10.0 mV, respectively. CytoViva ® microscopy images showed that LNC and AcE-LNC penetrated into SK-Mel-28 cells, and remained in the cytoplasm. AcE-LNC in vitro treatment (18–90×10 9 particles/mL; 1 hour) induced late apoptosis and necrosis; LNC and AcE-LNC (3–18×10 9 particles/mL; 48 hours) treatments reduced cell proliferation and delayed the cell cycle. Elevated levels of nitric oxide were found in supernatant of LNC and AcE-LNC, which were not dependent on nitric oxide synthase expressions. Daily intraperitoneal or oral treatment (days 3–10 after tumor injection) with LNC or AcE-LNC (1×10 12 particles/day), but not with AcE (50 mg/kg/day, same dose as AcE-LNC), reduced the volume of the tumor; nevertheless, intraperitoneal treatment caused toxicity. Oral LNC treatment was more efficient than AcE-LNC treatment. Moreover, oral treatment with nonencapsulated capric/caprylic triglyceride did not inhibit tumor development, implying that nanocapsule supramolecular structure is important to the therapeutic effects. Together, data herein presented highlight the relevance of the supramolecular structure of LNCs to toxicity on SK-Mel-28 cells and to the therapeutic efficacy on melanoma development in mice, conferring novel therapeutic mechanisms to LNC further than a drug delivery system.

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The yin and yang of nitric oxide in cancer progression

Cited by 318 publications

References 137 publications

Nitric Oxide Sensors for Biological Applications

Nitric Oxide Sensors for Biological Applications

Immune-associated proteins with potential in vivo anti-tumor activities are upregulated in lung cancer cells treated with umbelliprenin: A proteomic approach

Novel therapeutic mechanisms determine the effectiveness of lipid-core nanocapsules on melanoma models

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