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Positional isomerism markedly affects the growth inhibition of colon cancer cells by NOSH-aspirin: COX inhibition and modeling.

Vannini F, Chattopadhyay M, Kodela R, Rao PP, Kashfi K - Redox Biol (2015)

Bottom Line: We also analyzed the effect of these compounds on proliferation and apoptosis in HT-29 cells.The reduction of cell growth appeared to be mediated through inhibition of proliferation, and induction of apoptosis.These results suggest that the three positional isomers of NOSH-aspirin have the same biological actions, but that o-NOSH-ASA displayed the strongest anti-neoplastic potential.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Pharmacology and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, NY 10031, United States.

No MeSH data available.


Related in: MedlinePlus

The potential in vivo metabolites of o-, m-, p-NOSH-ASA derivatives.
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f0030: The potential in vivo metabolites of o-, m-, p-NOSH-ASA derivatives.

Mentions: Differential inhibition of COX-1 versus COX-2 might suggest adverse gastrointestinal side effects since that would lead to significantly lower PG levels within the gastric mucosa. However, we have shown that o-NOSH-ASA was devoid of any GI side effects even though it inhibited PGs within the gastric mucosa [13]. This observation is most likely due to the released NO and H2S which have been shown to be cytoprotective within the stomach [7–12]. Recently we also reported that positional isomers of aspirin (o-ASA, m-ASA, p-ASA) were equally potent in inhibiting colon cancer cell growth but had differences in the mode by which they inhibited COX-1 and COX-2 activity [23]. o-ASA (conventional aspirin) was shown to be an irreversible inhibitor of COX-1 and COX-2, whereas m-ASA and p-ASA were about 30–35% reversible. These data may also explain the differential IC50s seen in the present study for the positional isomers of NOSH-ASA. Also, based on the plausible metabolic pathway suggested (Fig. 6), it appears that these molecules may not be able to cause irreversible acetylation of Ser present in the COX active site. Additional studies are needed to determine the metabolites formed for these NOSH-aspirins.


Positional isomerism markedly affects the growth inhibition of colon cancer cells by NOSH-aspirin: COX inhibition and modeling.

Vannini F, Chattopadhyay M, Kodela R, Rao PP, Kashfi K - Redox Biol (2015)

The potential in vivo metabolites of o-, m-, p-NOSH-ASA derivatives.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4556775&req=5

f0030: The potential in vivo metabolites of o-, m-, p-NOSH-ASA derivatives.
Mentions: Differential inhibition of COX-1 versus COX-2 might suggest adverse gastrointestinal side effects since that would lead to significantly lower PG levels within the gastric mucosa. However, we have shown that o-NOSH-ASA was devoid of any GI side effects even though it inhibited PGs within the gastric mucosa [13]. This observation is most likely due to the released NO and H2S which have been shown to be cytoprotective within the stomach [7–12]. Recently we also reported that positional isomers of aspirin (o-ASA, m-ASA, p-ASA) were equally potent in inhibiting colon cancer cell growth but had differences in the mode by which they inhibited COX-1 and COX-2 activity [23]. o-ASA (conventional aspirin) was shown to be an irreversible inhibitor of COX-1 and COX-2, whereas m-ASA and p-ASA were about 30–35% reversible. These data may also explain the differential IC50s seen in the present study for the positional isomers of NOSH-ASA. Also, based on the plausible metabolic pathway suggested (Fig. 6), it appears that these molecules may not be able to cause irreversible acetylation of Ser present in the COX active site. Additional studies are needed to determine the metabolites formed for these NOSH-aspirins.

Bottom Line: We also analyzed the effect of these compounds on proliferation and apoptosis in HT-29 cells.The reduction of cell growth appeared to be mediated through inhibition of proliferation, and induction of apoptosis.These results suggest that the three positional isomers of NOSH-aspirin have the same biological actions, but that o-NOSH-ASA displayed the strongest anti-neoplastic potential.

View Article: PubMed Central - PubMed

Affiliation: Department of Physiology, Pharmacology and Neuroscience, Sophie Davis School of Biomedical Education, City University of New York Medical School, New York, NY 10031, United States.

No MeSH data available.


Related in: MedlinePlus