Extracellular ATP and Cancer—An Overview with Special Reference to P2 Purinergic Receptors

Deli, Tamás; Csernoch, László

doi:10.1007/s12253-008-9071-7

Cited by 74 publications

(68 citation statements)

References 95 publications

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“…In various tumour cell lines and tissues, notably melanoma cells (including A375), breast cancer or mouse glioma, (over)expression of P2X7 has been reported. In some cases, P2X7 activation by ATP causes a decrease in tumour cell number [30][31][32][33]. On the contrary, P2X7 activation may support cell proliferation, tumour growth or metastatic activity [34,35].…”

Section: Discussionmentioning

confidence: 99%

Natural compounds with P2X7 receptor-modulating properties

Fischer

Urban

Immig

et al. 2013

Purinergic Signalling

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The adenosine 5′-triphosphate (ATP)-gated P2X7 receptor is a membrane-bound, non-selective cation channel, expressed in a variety of cell types. The P2X7 senses high extracellular ATP concentrations and seems to be implicated in a wide range of cellular functions as well as pathophysiological processes, including immune responses and inflammation, release of gliotransmitters and cytokines, cancer cell growth or development of neurodegenerative diseases. In the present study, we identified natural compounds and analogues that can block or sensitize the ATP (1 mM)-induced Ca 2+ response using a HEK293 cell line stably expressing human P2X7 and fluorometric imaging plate reader technology. For instance, teniposide potently blocked the human P2X7 at sub-miromolar concentrations, but not human P2X4 or rat P2X2. A marked block of ATPinduced Ca 2+ entry and Yo-Pro-1 uptake was also observed in human A375 melanoma cells and mouse microglial cells, both expressing P2X7. On the other hand, agelasine (AGL) and garcinolic acid (GA) facilitated the P2X7 response to ATP in all three cell populations. GA also enhanced the YO-PRO-1 uptake, whereas AGL did not affect the ATP-stimulated intracellular accumulation of this dye. According to the pathophysiological role of P2X7 in various diseases, selective modulators may have potential for further development, e.g. as neuroprotective or antineoplastic drugs.

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Section: Discussionmentioning

confidence: 99%

Natural compounds with P2X7 receptor-modulating properties

Fischer

Urban

Immig

et al. 2013

Purinergic Signalling

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“…In any case, the denatured apyrase appeared to be a suitable control for bioactive apyrase in the present series of experiments. Extracellular/cell surface ATP has been studied in the male reproductive system and many nongametic systems and is thought to be an important regulatory and signaling factor [reviewed in Zhou et al 2007;Deli and Csernoch 2008]. Extracellular ATP likely has many different roles during sperm capacitation, acrosomal exocytosis, and fertilization.…”

Section: Discussionmentioning

confidence: 99%

Sperm-Surface ATP in Boar Spermatozoa is Required for Fertilization: Relevance to Sperm Proteasomal Function

Park

Kim

et al. 2009

Systems Biology in Reproductive Medicine

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Extracellular ATP has been implicated in a number of cellular events, including mammalian sperm function. The complement of ATP-dependent sperm proteins includes six subunits of the 26S proteasome, a multi-subunit protease specific to ubiquitinated substrate-proteins. Proteolysis of ubiquitinated proteins by the 26S proteasome is necessary for the success of mammalian fertilization, including but not limited to acrosomal exocytosis (AE) and spermzona pellucida (ZP) penetration. The 26S proteasome is uniquely present on the sperm acrosomal surface during mammalian, ascidian, and invertebrate fertilization. The proteasome is a multi-subunit protease complex of B2 MDa composed of the 19S regulatory complex and a 20S proteolytic core. Integrity of the 19S complex is maintained by six 19S ATPase subunits (PSMC1 through PSMC6). Consequently, we hypothesized that fertilization will be blocked by the depletion of sperm-surface associated ATP (ssATP). Depletion of ssATP by the Solanum tuberosum apyrase, a 49 kDa, non-cell permeant enzyme, significantly reduced the ATP content measured by an adapted luminescence-ATP assay from which all permeabilizing agents were excluded. Addition of active apyrase to porcine in vitro fertilization (IVF) medium caused a concentration dependent reduction in the overall fertilization rate. No such outcomes were observed in control groups using heat-inactivated apyrase. Apyrase treatment altered the band pattern of 19S ATPase subunits PSMC1 (Rpt2) and PSMC4 (Rpt3) in Western blotting, suggesting that it had an effect on the integrity of the sperm proteasomal 19S complex. Apyrase only altered the proteasomal core activities slightly, since these activities are not directly dependent on external ATP. In contrast, sperm treatment with MG132, a specific inhibitor of the proteasomal core chymotrypsin-like activity, inhibited the target proteolytic activity, but also induced a compensatory elevation in proteasomal peptidylglutamyl peptide hydrolase activity. Altogether, the present data provide an important missing piece of evidence in support of the ssATP-dependent, proteasomal-proteolytic model of sperm-ZP interactions.

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“…The effect of extracellular ATP on target tumor cells may have dosage dependence and tissue specificity, which constitutes its functional variation [6,[23][24][25][26]. One of the most important aspects of this field is the participation of eATP in determination of cell fate and its possible involvement in promoting, preventing, and treating malignancies [3,27]. Whether eATP has any functional role in determination of cell fate of anchorage-dependent and anchorageindependent hepatoma cells has not been clarified and is investigated in this study.…”

Section: Discussionmentioning

confidence: 99%

“…In response to tissue damage and cellular stress, intracellular ATP is actively released into the extracellular environment and acts as an important signaling molecule [1]. Extracellular ATP (eATP) exerts many functions in physiological and pathological conditions, and its effect on cells is mediated by ionotropic (P2X) and metabotropic (P2Y) receptors [2][3][4]. Extracellular ATP could be hydrolyzed by ectonucleotidases; thus, its concentration is maintained at very low level in physiological conditions [5].…”

Section: Introductionmentioning

confidence: 99%

High dose of extracellular ATP switched autophagy to apoptosis in anchorage-dependent and anchorage-independent hepatoma cells

Wei

Zhang

Xing

et al. 2013

Purinergic Signalling

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Extracellular adenosine triphosphate (eATP) transduces purinergic signal and plays an important regulatory role in many biological processes, including tumor cell growth and cell death. A large amount of eATP exists in the fast-growing tumor center and inflammatory tumor microenvironment. Tumor cells could acquire anoikis resistance and anchorage independence in tumor microenvironment and further cause metastatic lesion. Whether such a high amount of eATP has any effect on the anchored and nonanchored tumor cells in tumor microenvironment has not been elucidated and is investigated in this study. Our data showed that autophagy helped hepatoma cells to maintain survival under the treatment of no more than 1 mM of eATP. Only when eATP concentration reached a relatively high level (2.5 mM), cell organelle could not be further maintained by autophagy, and apoptosis and cell death occurred. In hepatoma cells under treatment of 2.5 mM of eATP, an AMP-activated protein kinase (AMPK) pathway was dramatically activated while mTOR signaling pathway was suppressed in coordination with apoptosis. Further investigation showed that the AMPK/mTOR axis played a key role in tipping the balance between autophagy-mediated cell survival and apoptosis-induced cell death under the treatment of eATP. This work provides evidence to explain how hepatoma cells escape from eATP-induced cytotoxicity as well as offers an important clue to consider effective manipulation of cancer.

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Extracellular ATP and Cancer—An Overview with Special Reference to P2 Purinergic Receptors

Cited by 74 publications

References 95 publications

Natural compounds with P2X7 receptor-modulating properties

Natural compounds with P2X7 receptor-modulating properties

Sperm-Surface ATP in Boar Spermatozoa is Required for Fertilization: Relevance to Sperm Proteasomal Function

High dose of extracellular ATP switched autophagy to apoptosis in anchorage-dependent and anchorage-independent hepatoma cells

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