Differential response of three cell types to dual stress of nitric oxide and radiation

Dhariwala, Fatema A.; Narang, Himanshi; Krishna, M. Bala

doi:10.1007/s10565-012-9213-2

Cited by 3 publications

(3 citation statements)

References 38 publications

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“…Additionally, a promising response rate of 75% was found with concurrent chemoradiation in a Phase 2 study in locally advanced NSCLC patients treated with cisplatin and vinorelbine plus concurrent nitroglycerin with radiotherapy [32] . The differences in observations between studies could be explained by tumor microenvironment heterogeneity and differences between tumor types [33] . These contradictory observations could be rationalized by a redistribution of blood flow through the ‘steal effect’, a consequence on blood flow of a systemic vasodilatory response as a result of the administration of a systemic NO donor.…”

Section: Indirect No Radiosensitization Effects: Increasing Tumor Oxymentioning

confidence: 98%

NO to cancer: The complex and multifaceted role of nitric oxide and the epigenetic nitric oxide donor, RRx-001

Scicinski¹,

Oronsky²,

Ning

et al. 2015

Redox Biology

107

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The endogenous mediator of vasodilation, nitric oxide (NO), has been shown to be a potent radiosensitizer. However, the underlying mode of action for its role as a radiosensitizer – while not entirely understood – is believed to arise from increased tumor blood flow, effects on cellular respiration, on cell signaling, and on the production of reactive oxygen and nitrogen species (RONS), that can act as radiosensitizers in their own right. NO activity is surprisingly long-lived and more potent in comparison to oxygen. Reports of the effects of NO with radiation have often been contradictory leading to confusion about the true radiosensitizing nature of NO. Whether increasing or decreasing tumor blood flow, acting as radiosensitizer or radioprotector, the effects of NO have been controversial. Key to understanding the role of NO as a radiosensitizer is to recognize the importance of biological context. With a very short half-life and potent activity, the local effects of NO need to be carefully considered and understood when using NO as a radiosensitizer. The systemic effects of NO donors can cause extensive side effects, and also affect the local tumor microenvironment, both directly and indirectly. To minimize systemic effects and maximize effects on tumors, agents that deliver NO on demand selectively to tumors using hypoxia as a trigger may be of greater interest as radiosensitizers. Herein we discuss the multiple effects of NO and focus on the clinical molecule RRx-001, a hypoxia-activated NO donor currently being investigated as a radiosensitizer in the clinic.

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Section: Indirect No Radiosensitization Effects: Increasing Tumor Oxymentioning

confidence: 98%

NO to cancer: The complex and multifaceted role of nitric oxide and the epigenetic nitric oxide donor, RRx-001

Scicinski¹,

Oronsky²,

Ning

et al. 2015

Redox Biology

107

View full text Add to dashboard Cite

show abstract

“…The exogenous NO was generated using a NO donor, S -nitroso- N -acetylpenicillamine (SNAP). SNAP could spontaneously release NO within 15 min upon light stimulation, and 100 μM of SNAP could generate ~27 μM of NO [17]. Zebrafish has become a popular vertebrate model in genetic, pharmacological and behavioral studies.…”

Section: Introductionmentioning

confidence: 99%

Exogenous Nitric Oxide Suppresses in Vivo X-ray-Induced Targeted and Non-Targeted Effects in Zebrafish Embryos

Kong

Yeung

Chan

et al. 2016

IJMS

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The present paper studied the X-ray-induced targeted effect in irradiated zebrafish embryos (Danio rerio), as well as a non-targeted effect in bystander naïve embryos partnered with irradiated embryos, and examined the influence of exogenous nitric oxide (NO) on these targeted and non-targeted effects. The exogenous NO was generated using an NO donor, S-nitroso-N-acetylpenicillamine (SNAP). The targeted and non-targeted effects, as well as the toxicity of the SNAP, were assessed using the number of apoptotic events in the zebrafish embryos at 24 h post fertilization (hpf) revealed through acridine orange (AO) staining. SNAP with concentrations of 20 and 100 µM were first confirmed to have no significant toxicity on zebrafish embryos. The targeted effect was mitigated in zebrafish embryos if they were pretreated with 100 µM SNAP prior to irradiation with an X-ray dose of 75 mGy but was not alleviated in zebrafish embryos if they were pretreated with 20 µM SNAP. On the other hand, the non-targeted effect was eliminated in the bystander naïve zebrafish embryos if they were pretreated with 20 or 100 µM SNAP prior to partnering with zebrafish embryos having been subjected to irradiation with an X-ray dose of 75 mGy. These findings revealed the importance of NO in the protection against damages induced by ionizing radiations or by radiation-induced bystander signals, and could have important impacts on development of advanced cancer treatment strategies.

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“…In our experiments with monocytes/macrophages, IR alone did activate HIV-1 LTR, but did not kill infected cells, which is consistent with previously published data about relative resistance of macrophages to cancer radiotherapy. 31,32 Nevertheless, the combination of moderate doses of IR with chemical compound, PKC agonist bryostatin 1, enhanced transcription activation and cell killing in monocyte/macrophages. 28 This suggests that the IR effect is cell-type specific and that infected T cells are more prone to apoptosis with IR, whereas IR with LRAs is needed to kill infected myeloid cells.…”

mentioning

confidence: 99%

Potential of Radiation-Induced Cellular Stress for Reactivation of Latent HIV-1 and Killing of Infected Cells

Iordanskiy

Kashanchi

2016

AIDS Research and Human Retroviruses

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The use of highly active antiretroviral therapy against HIV-1 for last two decades has reduced mortality of patients through extension of nonsymptomatic phase of infection. However, HIV-1 can be preserved in longlived resting CD4+ T cells, which form a viral reservoir in infected individuals, and potentially in macrophages and astrocytes. Reactivation of viral replication is critical since the host immune response in combination with antiretroviral therapy may eradicate the virus (shock and kill strategy). In this opinion piece, we consider potential application of therapeutic doses of irradiation, the well-known and effective stress signal that induces DNA damage and activates cellular stress response, to resolve two problems: activate HIV-1 replication and virion production in persistent reservoirs under cART and deplete infected cells through selective cell killing using DNA damage responses.

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Differential response of three cell types to dual stress of nitric oxide and radiation

Cited by 3 publications

References 38 publications

NO to cancer: The complex and multifaceted role of nitric oxide and the epigenetic nitric oxide donor, RRx-001

NO to cancer: The complex and multifaceted role of nitric oxide and the epigenetic nitric oxide donor, RRx-001

Exogenous Nitric Oxide Suppresses in Vivo X-ray-Induced Targeted and Non-Targeted Effects in Zebrafish Embryos

Potential of Radiation-Induced Cellular Stress for Reactivation of Latent HIV-1 and Killing of Infected Cells

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