Impairment of ATP-induced Ca2+-signalling in human thyroid cancer cells

Schöfl, Christof; Rössig, Lothar; Mader, T; Börger, Julia; Pötter, Eyck; Mühlen, A. von zur; Brabant, Georg

doi:10.1016/s0303-7207(97)00141-x

Cited by 11 publications

(3 citation statements)

References 22 publications

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“…SOCE activities were also reported in normal rat thyroid cell cultures (Marsigliante et al, 2002). The transformed and cancerous/undifferentiated thyrocytes were observed to have a disturbed or defective PLC-Ca 2ϩ signaling process after activation of the purinergic cascade (Schöfl et al, 1997;Elia et al, 2003;Yang et al, 2004).…”

mentioning

confidence: 90%

Clodronate-Induced Cell Apoptosis in Human Thyroid Carcinoma Is Mediated via the P2 Receptor Signaling Pathway

Yang

Teng²,

Chen³

et al. 2009

J Pharmacol Exp Ther

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Clodronate, a halogenated bisphosphonate, can inhibit the growth of human thyroid carcinoma (TC) cells. Previously, we found that a clodronate-induced Ca 2ϩ transient was correlated with clodronate-induced growth inhibition in TC cells. However, the details of the signaling process underlying the antiproliferative effect of clodronate on TC cells are not clear. In this study, we investigated the antiproliferative mechanism of clodronate on papillary TC (PTC) cells and xenotransplanted animals using a combination of pharmacological drugs. Reverse transcription-polymerase chain reaction analysis confirmed the endogenous expression of P2Y receptor isoforms in PTC cells. The P2 antagonist suramin not only inhibited the antiproliferative effect of clodronate and ATP on TC cells but also blocked all the Ca 2ϩ transients induced by clodronate and ATP. The release of Ca 2ϩ from the endoplasmic reticulum and membrane depolarization of mitochondria was observed during the clodronate-induced Ca 2ϩ transients. The results of terminal deoxynucleotidyltransferase dUTP nick-end labeling assays and flow cytometry with annexin V and caspase-3 staining suggest that both ATP and clodronate induce apoptosis. Significant inhibition of tumor invasion and colony formation was also observed in clodronate-treated PTC cells. We further demonstrated that only the cAMP inhibitor 9-(tetrahydro-2-furanyl)-9H-purin-6-amine (SQ22536), and not inhibitors of phospho-or store-operated Ca 2ϩ entry (2-aminoethyl diphenylborinate), can significantly reverse the effect of clodronate. Finally, in vivo animal and green fluorescent protein imaging studies further proved that the tumor inhibitory effect of clodronate on xenotransplanted CG3 cells can be reversed by treatment with suramin. In conclusion, we demonstrated that clodronate-induced PTC cell apoptosis and tumor inhibition are partially mediated by the P2Y receptorcAMP cascade.Papillary thyroid carcinoma (PTC) is one of the most commonly differentiated thyroid carcinomas (TCs) (Kondo et al., 2006;Kung et al., 2006). Genomic research has revealed that RET rearrangement and BRAF mutation are important in the carcinogenesis of TC/PTC (Lee et al., 1998;Kondo et al., 2006). Thus far, the treatment choice for TC is surgery in combination with postoperative radioiodine therapy (Huang et al., 2005). However, in patients with postoperative recurrent or lymphoid metastatic lesions without radioiodative uptake, the success of TC therapy is limited (Huang et al., 2005;Muresan et al., 2008).Anticancer or chemotherapeutic drugs are limited in effect and duration of response for the treatment of TC (Muresan et al., 2008). Recently, bisphosphonates (BPs) were found to have a broad range of in vivo and in vitro antitumor effects

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confidence: 90%

Clodronate-Induced Cell Apoptosis in Human Thyroid Carcinoma Is Mediated via the P2 Receptor Signaling Pathway

Yang

Teng²,

Chen³

et al. 2009

J Pharmacol Exp Ther

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“…Buna bir örnek olarak; tiroid kanser hücrelerinde P2Y reseptörleri yoluyla ATPindüklemeli Ca +2 sinyalizasyonu, normal insan tirositleri ile kıyaslandı¤ında SOCE aktivasyonunda ve IP3-ba¤ıntılı Ca +2 salınımı mekanizmasında spesifik azalma göstermektedir. [61] Özellikle büyük iletken Ca +2 -ba¤ımlı K + kanalı (BKCa) ve çeitli karsinojenler tarafından aktive oldu¤unda birçok anti-kanser proteininin transkripsiyonunu aktive eden ve büyüme blo¤u veya apoptozise neden olan p53 tümör-supresör transkripsiyon faktörü gibi di¤er önemli büyüme inhibitörü sinyaller arasındaki birlemelere neden olmaktadır. [62] ‹nsan HeLa servikal ve A2780 ovaryan kanser hücre hatlarında BKCa kanallarının farmakolojik blokajı, artmı p53 ekspresyonuyla beraber G 1 fazında hücre döngüsü blo¤unu ve apoptozu indüklemektedir.…”

Section: ‹Yon Kanalları Ve Metastazunclassified

Ion channels and cancer

Erdoğan¹

2018

FNG & Bilim Tıp Dergisi

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Ion channels are in the basic structural elements of living cells. In recent years it has emerged that ion channels have vital importance in tumor development and cancer progression. A series of genetic alterations that can affect the expression of ion channels or cause a change in ion channel activity occurs during transformation of a normal cell to the cancer. Ion channels are associated with cancer cell proliferation, apoptosis, migration, angiogenesis and metastasis. Ion channels still constitute a new field of research in oncology. Ultimately, a detailed understanding of the role of ion channels in key processes related to cancer will facilitate the development of molecular-targeted tools for diagnosis and treatment. Ion channels and cancer ÖZİyon kanalları yaşayan hücrelerin temel yapısal elemanları içindedir. Son yıllarda iyon kanallarının tümör gelişiminde ve kanserin ilerleyişinde hayati öneme sahip olduğu ortaya çıkmıştır. Normal bir hücrenin kansere dönüşümü sırasında iyon kanallarının ekspresyonunu etkileyebilen veya iyon kanal aktivitesinde bir değişime neden olabilen bir seri genetik değişim meydana gelmektedir. İyon kanalları kanser hücresinde proliferasyon, apoptoz, migrasyon, anjiyogenez ve metastaz ile ilişkilidir. İyon kanalları halen onkolojide yeni bir araştırma alanını oluşturmaktadır. Sonuçta iyon kanallarının kanserle ilgili anahtar süreçlerdeki rollerinin ayrıntılı bir şekilde anlaşılması, tanı ve tedavi için moleküler-hedefli araçların geliştirilmesini kolaylaştıracaktır.Anahtar sözcükler: Kanser; iyon kanalları; metastaz; yeni hedefler; proliferasyon.

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“…Loss of antithrombotic functions following EC activation may be applicable to the progression of both vasculitis and xenograft rejection ( 6 , − . One such regulated vascular thromboregulator is the ectoenzyme ATP diphosphohydrolase (ATPDase; EC 3.6.1.5 or CD39), previously designated as apyrase, ecto-ATPase, or ecto-ADPase ( , ).…”

mentioning

confidence: 99%

Suppression of ATP Diphosphohydrolase/CD39 in Human Vascular Endothelial Cells

et al. 1999

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Vascular ATP diphosphohydrolase/CD39 is an endothelial cell membrane protein with both ecto-ATPase and ecto-ADPase activities. Suppression of constitutive CD39 expression may result in elevated concentrations of ATP and ADP at the vascular interface that could predispose to thrombosis and inflammation. To study the effects of suppression of CD39 synthesis, stable 25-base antisense chimeric oligonucleotides targeting sequences at the 5' region of CD39 were designed. Transfection of these stable oligomers into cultured human endothelial cells resulted in dramatic decreases in levels of CD39 mRNA transcripts. Following transfection with antisense oligonucleotides, total ADPase activity fell from 26.0 +/- 3.1 in control cultures to 9.5 +/- 3.4 nmol of P(i) min(-1) (mg of protein)(-1) (p < 0.005); suppression of CD39 protein expression was also observed by Western blotting. Decreases in ATP diphosphohydrolase activity were associated with increases in concentrations of extracellular purine nucleotides released following stimulation of endothelial cells. Rates of initial hydrolysis of extracellular ATP released from purinergic agonist-stimulated endothelial cells decreased from 17.9 +/- 5.0 to 4.8 +/- 0.5 pmol min(-1) per 10(6) cells (p < 0.005) in antisense transfected cells. Therefore, CD39 regulates extracellular ATP concentrations and may be an important modulator of purinergic receptor activity in vascular endothelial cells.

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Impairment of ATP-induced Ca2+-signalling in human thyroid cancer cells

Cited by 11 publications

References 22 publications

Clodronate-Induced Cell Apoptosis in Human Thyroid Carcinoma Is Mediated via the P2 Receptor Signaling Pathway

Clodronate-Induced Cell Apoptosis in Human Thyroid Carcinoma Is Mediated via the P2 Receptor Signaling Pathway

Ion channels and cancer

Suppression of ATP Diphosphohydrolase/CD39 in Human Vascular Endothelial Cells

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