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Activated δ-opioid receptors inhibit hydrogen peroxide-induced apoptosis in liver cancer cells through the PKC/ERK signaling pathway
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Activated δ-opioid receptors inhibit hydrogen peroxide-induced apoptosis in liver cancer cells through the PKC/ERK signaling pathway
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Journal Article
Activated δ-opioid receptors inhibit hydrogen peroxide-induced apoptosis in liver cancer cells through the PKC/ERK signaling pathway
2014
Overview
Apoptotic liver cancer cells have important roles in liver tumorigenesis and liver cancer progression. Recent studies have shown that δ-opioid receptors are highly expressed in human liver and liver cancer cells. The present study aimed to investigate the role of activated δ-opioid receptors on human liver cancer cell apoptosis and its interrelation with the mitochondria and the protein kinase C/extracellular-signal-regulated kinase (PKC/ERK) signaling pathway. H2O2 was used to induce apoptosis in human liver cancer cells. During apoptosis, mitochondrial transmembrane potentials were observed to decrease, cytochrome c expression was found to increase and B cell lymphoma 2 (Bcl-2) expression decreased. These findings suggested that H2O2-induced apoptosis was mediated through the mitochondrial pathway. Of note, activated δ-opioid receptors were observed to inhibit H2O2-induced apoptosis in human liver cancer cells. Following δ-opioid receptor activation, the number of apoptotic liver cancer cells decreased, mitochondrial transmembrane potentials were restored, cytoplasmic cytochrome c and Bcl-2-associated X protein expression decreased and Bcl-2 expression increased. These data suggested that δ-opioid receptor activation inhibited mitochondria-mediated apoptosis. In addition, activation of δ-opioid receptors was observed to increase the expression of PKC and ERK in human liver cancer cells. Furthermore, upon inhibition of the PKC/ERK signaling pathway, the protective effect associated with the δ-opioid receptor on liver cancer cell apoptosis was inhibited, which was not associated with the status of δ-opioid receptor activation. These findings suggested that the PKC/ERK signaling pathway has an important role in δ-opioid receptor-mediated inhibition of apoptosis in human liver cancer cells.
Publisher
D.A. Spandidos,Spandidos Publications,Spandidos Publications UK Ltd
Subject
/ bcl-2-Associated X Protein - metabolism
/ Extracellular signal-regulated kinase
/ Extracellular Signal-Regulated MAP Kinases - metabolism
/ Humans
/ Hydrogen Peroxide - toxicity
/ Ischemia
/ Kinases
/ Liver Neoplasms - metabolism
/ Lymphoma
/ Membrane Potential, Mitochondrial - drug effects
/ Opioids
/ Protein Kinase C - metabolism
/ Proteins
/ Proto-Oncogene Proteins c-bcl-2 - metabolism
/ Receptors, Opioid, delta - antagonists & inhibitors
/ Receptors, Opioid, delta - metabolism
/ Rodents
/ Signal Transduction - drug effects
/ Studies
