Extracellular adenosine induces apoptosis in Caco-2 human colonic cancer cells by activating caspase-9/-3 via A2a adenosine receptors

Yasuda, Yoh; Saito, Masaru; Yamamura, Takehira; Yaguchi, Takahiro; Nishizaki, Tomoyuki

doi:10.1007/s00535-008-2273-7

Cited by 67 publications

(55 citation statements)

References 42 publications

(44 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adenosine has also been shown to downregulate expression of the anti-apoptotic factor Bcl-xl, and upregulate the expression of the pro-apoptotic factor BH3 interacting-domain death agonist via the A 2a adenosine receptor, thereby disrupting mitochondrial membrane potentials to facilitate the efflux of cytochrome c from the mitochondria into the cytosol to activate caspase-9 and -3 in human liver cancer HepG2 cells (25). Similarly, adenosine has been reported to induce apoptosis in human colon cancer CW2 and Caco-2 cells by activating the cleavage of caspase-9, -3, and PARP via the A 1 and A 2a receptors (26,27). Adenosine treatment in the present study increased the protein expression of the pro-apoptotic factor Bax whereas that of the anti-apoptotic factor Bcl-2 was markedly decreased, with the release of cytochrome c into the cytosol was stimulated in FaDu cells.…”

Section: Discussionmentioning

confidence: 99%

Adenosine induces intrinsic apoptosis via the PI3K/Akt/mTOR signaling pathway in human pharyngeal squamous carcinoma FaDu cells

et al. 2018

View full text Add to dashboard Cite

Adenosine has been identified to occur abundantly intra-and extracellularly, and to exert diverse biological functions, including the suppression of cell proliferation and the induction of apoptosis. Adenosine has been reported to induce apoptosis in several cancer cell lines; however, to the best of our knowledge, the effect of adenosine on head and neck cancer cells has not been investigated. Therefore, the purpose of the present study was to evaluate whether adenosine exerts any anticancer effect via induction of apoptosis in human pharyngeal squamous carcinoma FaDu cells. An MTT assay demonstrated that adenosine-treated FaDu cells inhibited a dose-dependent rate of cell growth, whereas human oral keratinocytes cells were unaffected by adenosine treatment. In addition, A and A adenosine receptor mRNA was detected in FaDu cells by reverse transcription-polymerase chain reaction, and adenosine-induced FaDu cell death was significantly suppressed by treatment with ATL-444, an antagonist of these receptors. Furthermore, adenosine-induced cell growth inhibition was exerted via apoptosis, as confirmed by the analysis of DNA fragmentation, Hoechst nuclear staining and flow cytometry with Annexin V-fluorescein isothiocyanate and propidium iodide staining. Adenosine was also demonstrated to induce an increase in Bcl-associated X expression, a decrease in B-cell lymphoma 2 expression, the release of cytochrome c from mitochondria, and the activation of caspase-3, -9 and poly(ADP-ribose) polymerase in FaDu cells. Finally, phosphoinositide 3-kinase (PI3K), RAC serine/threonine-protein kinase (Akt) and mechanistic target of rapamycin (mTOR) phosphorylation was found to be significantly inhibited in adenosine-treated FaDu cells, as was phosphorylation of the mTOR downregulators, S6 kinase β1, eukaryotic translation initiation factor 4E-binding protein 1, and eukaryotic translation initiation factor 4 γ1. Taken together, these results indicate that adenosine induces apoptosis via the mitochondrial intrinsic pathway, and activates caspase-3 and -9 activity via the PI3K/Akt/mTOR signaling pathway.

show abstract

Section: Discussionmentioning

confidence: 99%

Adenosine induces intrinsic apoptosis via the PI3K/Akt/mTOR signaling pathway in human pharyngeal squamous carcinoma FaDu cells

et al. 2018

View full text Add to dashboard Cite

show abstract

“…The A 3 receptor agonist CF101 stabilised the tumour in 35 % of the patients with refractory metastatic colorectal cancer in a phase II, multi-centre study [642]. Adenosine has been claimed to induce apoptosis in Caco-2 colonic cancer cell [735]. Adenosine upregulates CXCR4, which is a chemokine receptor that plays a crucial role in determining the ability of cancer cells to metastasize from the primary tumour.…”

Section: Injurymentioning

confidence: 99%

Purinergic signalling in the gastrointestinal tract and related organs in health and disease

Burnstock

2013

Purinergic Signalling

View full text Add to dashboard Cite

Purinergic signalling plays major roles in the physiology and pathophysiology of digestive organs. Adenosine 5′-triphosphate (ATP), together with nitric oxide and vasoactive intestinal peptide, is a cotransmitter in nonadrenergic, non-cholinergic inhibitory neuromuscular transmission. P2X and P2Y receptors are widely expressed in myenteric and submucous enteric plexuses and participate in sympathetic transmission and neuromodulation involved in enteric reflex activities, as well as influencing gastric and intestinal epithelial secretion and vascular activities. Involvement of purinergic signalling has been identified in a variety of diseases, including inflammatory bowel disease, ischaemia, diabetes and cancer. Purinergic mechanosensory transduction forms the basis of enteric nociception, where ATP released from mucosal epithelial cells by distension activates nociceptive subepithelial primary afferent sensory fibres expressing P2X3 receptors to send messages to the pain centres in the central nervous system via interneurons in the spinal cord. Purinergic signalling is also involved in salivary gland and bile duct secretion.

show abstract

“…Protein concentration was assessed by the Bradford method, and caspase activity was assayed using a fluorometric method as previously reported [19], in a luminescence spectrometer (Sinergy HT, BioTek) at 380/430-460 nm. Acetyl tetrapeptides coupled to 4-methycoumaryl-7-amide were used as substrates: Ac-DEVD-AMC (caspase-3/7/8) and Ac-LEHD-AMC(caspase-9) (PeptaNova GmdH, Sandhausen, Germany).…”

Section: Caspase Activitymentioning

confidence: 99%

Dehydroepiandrosterone has strong antifibrotic effects and is decreased in idiopathic pulmonary fibrosis

et al. 2012

View full text Add to dashboard Cite

Idiopathic pulmonary fibrosis (IPF) is an ageing-related lung disorder characterised by expansion of the myofibroblast population and aberrant lung remodelling. Dehydroepiandrosterone (DHEA), a steroid pro-hormone, decreases with age but an exaggerated decline has been associated with chronic degenerative diseases.We quantified the plasma levels of DHEA and its sulfated form (DHEA-S) in 137 IPF patients and 58 controls and examined the effects of DHEA on human lung fibroblasts.Plasma DHEA/DHEA-S was significantly decreased in male IPF patients (median (range) DHEA: 4.4 (0.2–29.2)versus6.7 (2.1–15.2) ng·mL−1, p<0.01; DHEA-S: 47 (15.0–211)versus85.2 (37.6–247.0) μg·dL−1, p<0.001), while in females only DHEA-S was significantly decreased (32.6 (15.0–303.0)versus68.3 (16.4–171) μg·dL−1, p<0.001). DHEA caused a decrease in fibroblast proliferation and an approximately two-fold increase in fibroblast apoptosis, probably through the intrinsic pathway with activation of caspase-9. This effect was accompanied by upregulation of several pro-apoptotic proteins (Bax and cyclin-dependent kinase-inhibitor CDNK1A) and downregulation of anti-apoptotic proteins, such as cellular inhibitor of apoptosis (c-IAP)1 and c-IAP2. DHEA also caused a significant decrease of transforming growth factor-β1-induced collagen production and fibroblast to myofibroblast differentiation, and inhibited platelet-derived growth factor-induced fibroblast migration.These findings demonstrate a disproportionate decrease of DHEA/DHEA-S in IPF patients and indicate that this molecule has multiple antifibrotic properties.

show abstract

Extracellular adenosine induces apoptosis in Caco-2 human colonic cancer cells by activating caspase-9/-3 via A2a adenosine receptors

Abstract: Extracellular adenosine induces apoptosis in Caco-2 cells by activating caspase-9 and the downstream effector caspase caspase-3 in association with mitochondrial damage via A(2a) adenosine receptors.

Cited by 67 publications

References 42 publications

Adenosine induces intrinsic apoptosis via the PI3K/Akt/mTOR signaling pathway in human pharyngeal squamous carcinoma FaDu cells

Adenosine induces intrinsic apoptosis via the PI3K/Akt/mTOR signaling pathway in human pharyngeal squamous carcinoma FaDu cells

Purinergic signalling in the gastrointestinal tract and related organs in health and disease

Dehydroepiandrosterone has strong antifibrotic effects and is decreased in idiopathic pulmonary fibrosis

Contact Info

Product

Resources

About