Rapid chemosensitivity assay with human normal and tumor cells in vitro

Dietary oxysterols are cholesterol auto-oxidation products widely present in cholesterol-rich foods.They are thought to affect the intestinal barrier function, playing a role in gut inflammation. This study has characterized specific cell signals that are up-regulated in differentiated CaCo-2 colonic epithelial cells by a mixture of oxysterols representative of a hyper-cholesterolemic diet. p38 MAPK activation plays a major role, while other signal branches, i.e. the JNK and ERK pathways, make minor contributions to the intestinal inflammation induced by dietary oxysterols. p38 transduction might be the missing link connecting the known NADPH oxidase activation, and the induction of NF-κB-dependent inflammatory events related to oxysterols' action in the intestine. A NOX1/p38 MAPK/NF-κB signaling axis was demonstrated by the quenched inflammation observed on blocking individual branches of this signal with specific chemical inhibitors. Further, all these signaling sites were prevented when CaCo-2 cell were pre-incubated with phenolic compounds extracted from selected wines made of typical Sardinian grape varieties: red Cannonau and white Vermentino. Notably, Cannonau was more effective than Vermentino. The effect of Sardinian wine extracts on intestinal inflammation induced by dietary oxysterols might mainly be due to their phenolic content, more abundant in Cannonau than in Vermentino. Furthermore, among different phenolic components of both wines, epicatechin and caffeic acid exerted the strongest effects. These findings show a major role of the NOX1/p38 MAPK/NF-κB signaling axis in the activation of oxysteroldependent intestinal inflammation, and confirm the concept that phenolics act as modulators at different sites of pro-oxidant and pro-inflammatory cell signals.

show abstract

“…Percentage of cell death in term of % LDH release ( 21 Results were expressed as % of cell viability ( Table 1).…”

Section: Evaluation Of Cell Death and Viabilitymentioning

confidence: 99%

The role of p38 MAPK in the induction of intestinal inflammation by dietary oxysterols: modulation by wine phenolics

et al. 2015

View full text Add to dashboard Cite

show abstract

“…12) IC 50 values were determined from logarithmic graphs of growth inhibition versus concentration. Doxorubicin was used as a positive control, while DMSO was used as the vehicle control.…”

Section: Plant Materialsmentioning

confidence: 99%

Antileishmanial Activity of Natural Diterpenes from Cistus sp. and Semisynthetic Derivatives Thereof

Fokialakis

Kalpoutzakis

Tekwani

et al. 2006

Biological & Pharmaceutical Bulletin

View full text Add to dashboard Cite

“…The neutral red (NR) assay was performed as described by Borenfreund et al (1990). Gelatinized, flat-bottom, 96-well plates (Costar) were seeded with 4 × 10 3 cells per well and incubated for 18 h at 37°C.…”

Section: Huvec Neutral Red Assaymentioning

confidence: 99%

In vivo and in vitro evaluation of combretastatin A-4 and its sodium phosphate prodrug

et al. 1999

View full text Add to dashboard Cite

SummaryThe anti-tumour effects and mechanism of action of combretastatin A-4 and its prodrug, combretastatin A-4 disodium phosphate, were examined in subcutaneous and orthotopically transplanted experimental colon tumour models. Additionally, the ability of these compounds to directly interfere with endothelial cell behaviour was also examined in HUVEC cultures. Combretastatin A-4 (150 mg kg -1 , intraperitoneally (i.p.)) and its water-soluble prodrug (100 mg kg -1 , i.p.) caused almost complete vascular shutdown (at 4 h), extensive haemorrhagic necrosis which started at 1 h after treatment and significant tumour growth delay in MAC 15A subcutaneous (s.c.) colon tumours. Similar vascular effects were obtained in MAC 15 orthotopic tumours and SW620 human colon tumour xenografts treated with the prodrug. More importantly, in the orthotopic models, necrosis was seen in vascularized metastatic deposits but not in avascular secondary deposits. The possible mechanism giving rise to these effects was examined in HUVEC cells. Here cellular networks formed in type I calf-skin collagen layers and these networks were completely disrupted when incubated with a non-cytotoxic concentration of combretastatin A-4 or its prodrug. This effect started at 4 h and was complete by 24 h. The same non-cytotoxic concentrations resulted in disorganization of F-actin and β-tubulin at 1 h after treatment. In conclusion, combretastatin A-4 and its prodrug caused extensive necrosis in MAC 15A s.c. and orthotopic colon cancer and metastases, resulting in anti-tumour effects. Necrosis was not seen in avascular tumour nodules, suggesting a vascular mechanism of action.

show abstract

Rapid chemosensitivity assay with human normal and tumor cells in vitro

Cited by 157 publications

References 14 publications

The role of p38 MAPK in the induction of intestinal inflammation by dietary oxysterols: modulation by wine phenolics

The role of p38 MAPK in the induction of intestinal inflammation by dietary oxysterols: modulation by wine phenolics

Antileishmanial Activity of Natural Diterpenes from Cistus sp. and Semisynthetic Derivatives Thereof

In vivo and in vitro evaluation of combretastatin A-4 and its sodium phosphate prodrug

Contact Info

Product

Resources

About