Nitric Oxide and the Regulation of Apoptosis in Tumour Cells

Tarr, Joanna M.; Eggleton, Paul; Winyard, Paul G.

doi:10.2174/138161206779010477

Cited by 38 publications

(26 citation statements)

References 267 publications

(341 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, ϳ50% of all cancers have mutated or deficient p53, and one could hypothesize utilizing NO as a chemotherapeutic agent in this setting. Several groups have already begun to examine the use of different NO-donating compounds to induce apoptosis in several different cancer cell lines in vitro and in vivo (29,44).…”

Section: Discussionmentioning

confidence: 99%

Regulation of reactive oxygen species by p53: implications for nitric oxide-mediated apoptosis

Popowich

Vavra

Walsh

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

Section: Discussionmentioning

confidence: 99%

Regulation of reactive oxygen species by p53: implications for nitric oxide-mediated apoptosis

Popowich

Vavra

Walsh

et al. 2010

American Journal of Physiology-Heart and Circulatory Physiology

View full text Add to dashboard Cite

show abstract

“…The combined organic layer was dried with Na 2 SO 4 and evaporated to afford a residue that was purified by flash chromatography to afford the nitrile (275 mg, 83%). 1 The viability of the cells, seeded in flat-bottomed 96-well plates (1 Â 10 4 cells per well) and after 24 h of incubation in the presence of different concentration of either VGX-1027 or GIT-27NO, was assessed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test or crystal violet staining for adherent cells as described previously (19). The results are presented as percentage of control values obtained in untreated cultures.…”

Section: Synthesis Of Git-27nomentioning

confidence: 99%

“…Nitric oxide (NO) is a highly reactive molecule implicated in numerous physiologic and pathologic processes, which plays an important role in nonspecific antitumor immune response (1,2). However, in some circumstances, NO may also lead to tumor expansion and metastases (1,3,4).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Anticancer properties of the novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide in vitro and in vivo

Maksimović‐Ivanić

Mijatović

Harhaji

et al. 2008

Molecular Cancer Therapeutics

View full text Add to dashboard Cite

Preclinical studies have shown that nitric oxide (NO) -donating nonsteroidal anti-inflammatory drugs possess anticancer activities. Here, we report in vitro and in vivo studies showing the antitumor effect of the NO-donating isoxazole derivative (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid (GIT-27NO). GIT-27NO, but not the NOdeprived parental compound VGX-1027, significantly affected viability of both rodent (L929, B16, and C6) and human (U251, BT20, HeLa, and LS174) tumor cell lines. GIT-27NO triggered either apoptotic cell death (e.g., L929 cells) or autophagic cell death (C6 and B16 cells). Moreover, GIT-27NO hampered the viability of cisplatinresistant B16 cells. NO scavenger hemoglobin completely prevented GIT-27NO-induced death, indicating that NO release mediated the tumoricidal effect of the compound. Increase in intracellular NO upon on the treatment was associated with intensified production of reactive oxygen species, whereas their neutralization by antioxidant N-acetylcysteine resulted in partial recovery of cell viability. The antitumor activity of the drug was mediated by the selective activation of mitogen-activated protein kinases in a cell-specific manner and was neutralized by their specific inhibitors. In vivo treatment with GIT-27NO significantly reduced the B16 melanoma growth in syngeneic C57BL/6 mice. The therapeutic effect occurred at dose (0.5 mg/mouse) up to 160 times lower than those needed to induce acute lethality (80 mg/mouse). In addition, a dose of GIT-27NO five times higher than that found effective in the melanoma model was well tolerated by the mice when administered for 4 consecutive weeks. These data warrant additional studies to evaluate the possible translation of these findings to the clinical setting.

show abstract

“…2 It has been well studied that RNS-induced apoptosis is executed via the following two main mechanisms: (i) mitochondria-dependent intrinsic apoptosis pathway and (ii) DNA damage and p53 activation. 3 In contrast, the signalling pathways controlling RNS-induced non-apoptotic or necrotic cell death are less studied. There is evidence suggesting that RNS impair the respiratory function of mitochondria and ATP production and eventually lead to necrosis.…”

mentioning

confidence: 99%

Signaling pathways from membrane lipid rafts to JNK1 activation in reactive nitrogen species-induced non-apoptotic cell death

Zhang

et al. 2007

Cell Death Differ

View full text Add to dashboard Cite

At present, the signaling pathways controlling reactive nitrogen species (RNS)-induced non-apoptotic cell death are relatively less understood. In this work, various RNS donors are found to induce caspase-independent non-apoptotic cell death in mouse embryonic fibroblasts (MEF). In search of the molecular mechanisms, we first established the role of c-Jun N-terminal kinase (JNK) in RNS-induced non-apoptotic cell death. RNS readily activate JNK, and the jnk1À/À MEF are resistant to RNS-induced cell death. Moreover, the reconstitution of JNK1 effectively restores the sensitivity to RNS. Next, we identified tumor necrosis factor receptor-associated factor 2 (TRAF2) and apoptosis signal-regulating kinase 1 (ASK1) as the essential upstream molecules for RNS-induced JNK activation and cell death. RNS fail to activate JNK and induce cell death in traf2À/À MEF; and reconstitution of TRAF2 effectively restores the responsiveness of traf2À/À MEF to RNS. Moreover, RNS-induced ASK1 activation is impaired in traf2À/À cells and overexpression of a mutant ASK1 protein suppresses RNS-induced cell death in wild-type MEF cells. Last, we explored the signaling events upstream of TRAF2 and found that translocation of TRAF2 and JNK1 onto membrane lipid rafts is required for RNS-mediated JNK1 activation and cell death. Taken together, data from our study reveal a novel signaling pathway regulating RNS-induced JNK1 activation and non-apoptotic cell death.

show abstract

Nitric Oxide and the Regulation of Apoptosis in Tumour Cells

Cited by 38 publications

References 267 publications

Regulation of reactive oxygen species by p53: implications for nitric oxide-mediated apoptosis

Regulation of reactive oxygen species by p53: implications for nitric oxide-mediated apoptosis

Anticancer properties of the novel nitric oxide-donating compound (S,R)-3-phenyl-4,5-dihydro-5-isoxazole acetic acid-nitric oxide in vitro and in vivo

Signaling pathways from membrane lipid rafts to JNK1 activation in reactive nitrogen species-induced non-apoptotic cell death

Contact Info

Product

Resources

About