The opioid growth factor-opioid growth factor receptor axis regulates cell proliferation of human hepatocellular cancer

Avella, Diego M.; Kimchi, Eric T.; Donahue, Renee N.; Tagaram, Hephzibah Rani S.; McLaughlin, Patricia J.; Zagon, Ian S.; Staveley-O’Carroll, Kevin F.

doi:10.1152/ajpregu.00646.2009

Cited by 38 publications

(35 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…3 Although enkephalins bind to other opioid receptors, data from many studies support that OGF is interacting through OGFr to mediate its repressive action on human cancer cell lines. 4,8,9 The MDA-MB-231 cell lines that were transiently transfected with OGFr siRNA responded to a partial knockdown of the OGFr by acceleration in growth, and within 72 h more cells were reported than in control cultures. Addition of exogenous OGF which normally reduced cell number by $20% had no inhibitory effect.…”

Section: Discussionmentioning

confidence: 99%

Opioid growth factor – opioid growth factor receptor axis inhibits proliferation of triple negative breast cancer

Zagon

Porterfield

McLaughlin

2013

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

Triple negative breast cancer (TNBC) represents approximately 15% of the newly diagnosed cancers worldwide and is characterized by tissue lacking in estrogen, progesterone and human epidermal growth factor receptors. TNBC disproportionately affects younger women and women of colour, and new treatments are needed. The opioid growth factor (OGF) - opioid growth factor receptor (OGFr) axis is a determinant of cell proliferation in neoplasia, and OGF is an endogenously produced pentapeptide that inhibits cell replication by interacting with OGFr and upregulating cyclin-dependent inhibitory kinase pathways thus reducing DNA synthesis. In these studies we investigated the presence and function of the OGF-OGFr axis in two human TNBC cell lines, as well as in breast cancer cell lines containing hormonal receptors. TNBC cell lines MDA-MD-231 and BT-20, as well as human breast cancer cells SK-BR-3 and MCF-7, were examined for the presence of pentapeptide and receptors, as well as their response to OGF. Specificity of peptide and receptor was confirmed by antibody neutralization and molecular studies to knockdown classical receptor protein. The requirement for protein transcription and translation and RNA transcription were investigated. Growth of TNBC cells in the presence of OGF and standard of care chemotherapeutic agent paclitaxel was evaluated to determine both efficacy and protective effects against toxicity. OGF treatment inhibited TNBC cells in a dosage related, receptor mediated, and reversible manner. OGF was the specific endogenous opioid to inhibit cell proliferation, and this was mediated by p21 cyclin dependent inhibitory kinase pathways, and required protein and RNA synthesis. OGFr was the specific receptor involved; both peptide and receptor were detected in all four cell lines. OGF treatment inhibited growth of all cancer cell lines evaluated, and reduced cell death in cultures exposed to paclitaxel. The OGF-OGFr axis is present and functioning in TNBC cell lines, and provides a novel biological pathway as potential therapy.

show abstract

Section: Discussionmentioning

confidence: 99%

Opioid growth factor – opioid growth factor receptor axis inhibits proliferation of triple negative breast cancer

Zagon

Porterfield

McLaughlin

2013

Exp Biol Med (Maywood)

View full text Add to dashboard Cite

show abstract

“…For example, δ-opioid receptors were found to have a protective role against liver damage in an animal model of cholestasis (32). In addition, endogenous opioid growth factor promotes the proliferation of liver cancer cells (10). These protective effects are attributed to the activation of the δ-opioid receptor on liver cell membranes.…”

Section: Discussionmentioning

confidence: 99%

“…In addition to the central nervous system and heart, δ-opioid receptors are abundantly expressed in the liver (8,9). It has been recently discovered that the δ-opioid receptor affects the generation and progression of hepatic tumors, viral hepatitis, liver cirrhosis and other diseases (10,11).…”

Section: Introductionmentioning

confidence: 99%

Activation of the δ-opioid receptor inhibits serum deprivation-induced apoptosis of human liver cells via the activation of PKC and the mitochondrial pathway

Wang¹

2011

Int J Mol Med

View full text Add to dashboard Cite

Abstract. Apoptosis of human liver cells is commonly found in liver diseases and liver surgery and directly affects their prognosis. Recent studies have found that δ-opioid receptors, abundant in the membranes of hepatic cells, participate in the oncogenesis and progression of liver tumors, viral hepatitis, liver cirrhosis and other diseases. The purpose of this study was to analyze the effect of the activation of the δ-opioid receptor on liver cell apoptosis and explore its relationship with PKC and the mitochondrial pathway. Hepatic cells were serum-deprived to induce apoptosis in vitro. During the period of apoptosis, mitochondrial membrane potential decreased, protein levels of cytosolic cytochrome c increased and the expression of Bcl-2 decreased, indicating that apoptosis was specifically induced by the mitochondrial pathway. Importantly, activation of δ-opioid receptors reversed the apoptotic state of hepatic cells. Following δ-opioid receptor activation, the mitochondrial membrane potential remained stable, and the expression of cytosolic cytochrome c and Bax decreased. These data suggest that δ-opioid receptor activation specifically inhibits the mitochondrial apoptotic pathway. In addition, activation of the δ-opioid receptor apparently increased the levels of PKC; blocking the PKC pathway led to increased apoptosis of liver cells, which was not affected by the activation of δ-opioid receptor. Blocking the PKC pathway led to increased apoptosis of liver cells, which was associated with δ-opioid receptor activation. Therefore, the PKC pathway is involved in the anti-apoptotic effects of the δ-opioid receptor on liver cells.

show abstract

“…It has also been shown that opioid use may have toxic effects on the central and peripheral nervous systems, leading to irreversible, pathological cellular changes. Furthermore, heroin and other opioids have been shown to inhibit the synthesis of DNA and RNA in brain tissues (Avella et al, 2010;McLaughlin, Zagon, 2012). Our results indicate that the effect of heroin on the metabolism of purine nucleotides may result in purine nucleotide deficiency in the brain, representing a putative biochemical mechanism of heroin addiction.…”

Section: Content Detection Of Purine Nucleotidesmentioning

confidence: 68%

Effects of purine nucleotide administration on purine nucleotide metabolism in brains of heroin-dependent rats

Zhang

Chen

et al. 2016

Braz. J. Pharm. Sci.

View full text Add to dashboard Cite

Heroin is known to enhance catabolism and inhibit anabolism of purine nucleotides, leading to purine nucleotide deficiencies in rat brains. Here, we determined the effect of exogenous purine nucleotide administration on purine nucleotide metabolism in the brains of heroin-dependent rats. Heroin was administrated in increasing doses for 9 consecutive days to induce addiction, and the biochemical changes associated with heroin and purine nucleotide administration were compared among the treated groups. HPLC was performed to detect the absolute concentrations of purine nucleotides in the rat brain cortices. The enzymatic activities of adenosine deaminase (ADA) and xanthine oxidase (XO) in the treated rat cortices were analyzed, and qRT-PCR was performed to determine the relative expression of ADA, XO, adenine phosphoribosyl transferase (APRT), hypoxanthine-guaninephosphoribosyl transferase (HGPRT), and adenosine kinase (AK). Heroin increased the enzymatic activity of ADA and XO, and up-regulated the transcription of ADA and XO. Alternatively, heroin decreased the transcription of AK, APRT, and HGPRT in the rat cortices. Furthermore, purine nucleotide administration alleviated the effect of heroin on purine nucleotide content, activity of essential purine nucleotide metabolic enzymes, and transcript levels of these genes. Our findings therefore represent a novel, putative approach to the treatment of heroin addiction. Uniterms:Purine nucleotide/quantitative analysis. Purine nucleotide/effects/brain rats. Heroin analysis. Adenosine deaminase analysis. Xanthine oxidase analysis INTRODUCTIONOpiates, such as morphine and heroin, are illegally used as recreational drugs worldwide, and can significantly impair the user's physical and mental health (Chu et al., 2009;Li et al., 2014). Opioid dependence is a significant public health concern, underscoring the need for effective treatment options (Kresina, Bruce, Mulvey, 2013;Nutt, King, Phillips, 2010). Therefore, the exploration of the effects of repeated exposure to these compounds is important for understanding the mechanisms of drug dependency and developing new treatment options.Properly regulated purine nucleotide (PN) metabolism is necessary for normal brain function (Franke, 2011). Imbalances in purine nucleotide levels lead to a variety of human diseases (Burhans, Weinberger, 2007;El-Hattab, Scaglia, 2013;Kimura et al., 2003). Studies have shown that morphine and heroin can enhance the oxidation of xanthine and hypoxanthine in the lobus temporalis, lobus frontalis, and lobus parietalis of rats (Liu et al., 2007;Yang et al., 2006). Uric acid (UA) is the final oxidation product of purine metabolism in humans and higher primates, and changes in UA levels may reflect the catabolism of purine nucleotides (Liang, Clark, 2004). Furthermore, it has been reported that morphine may increase UA concentrations in the corpus striatum, as well as in serum and extracellularly, in vitro (Enrico et al., 1997;Sumathi, Niranjali Devaraj, 2009). In patients where morphine was administe...

show abstract

The opioid growth factor-opioid growth factor receptor axis regulates cell proliferation of human hepatocellular cancer

Cited by 38 publications

References 35 publications

Opioid growth factor – opioid growth factor receptor axis inhibits proliferation of triple negative breast cancer

Opioid growth factor – opioid growth factor receptor axis inhibits proliferation of triple negative breast cancer

Activation of the δ-opioid receptor inhibits serum deprivation-induced apoptosis of human liver cells via the activation of PKC and the mitochondrial pathway

Effects of purine nucleotide administration on purine nucleotide metabolism in brains of heroin-dependent rats

Contact Info

Product

Resources

About