Therapeutic potency of pharmacological adenosine receptors agonist/antagonist on cancer cell apoptosis in tumor microenvironment, current status, and perspectives

Soleimani, Anvar; Bahreyni, Amirhossein; Roshan, Mostafa Karimi; Soltani, Arash; Ryzhikov, Mikhail; Shafiee, Mojtaba; Soukhtanloo, Mohammad; Jaafari, Mahmoud Reza; Mashkani, Baratali; Hassanian, Seyed Mahdi

doi:10.1002/jcp.27249

Cited by 26 publications

(20 citation statements)

References 80 publications

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“…We also detected the tumor metastasis–related matrix metalloproteinases (MMPs) and found that adenosine increased MMP-2, MMP-7, MMP-9, and MMP-13 expression in the MKN45 cells, but that SCH 58261 blocked this effect (Figure 2D). However, the expression of MMP9, 48 h and 72 h decreased slightly more than 24 h, which may be related to adenosine-induced tumor cell apoptosis (Sargazi et al , 2019; Soleimani et al , 2019). Collectively, these findings demonstrate that adenosine promotes tumor invasion and metastasis in GC through the A2aR pathway.…”

Section: Resultsmentioning

confidence: 95%

Adenosine interaction with adenosine receptor A2a promotes gastric cancer metastasis by enhancing PI3K–AKT–mTOR signaling

Shi

Miao

et al. 2019

MBoC

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The accumulation of adenosine in the tumor microenvironment is associated with tumor progression in many cancers. However, whether adenosine is involved in gastric cancer (GC) metastasis and progression, and the underlying molecular mechanism, is largely unclear. In this study, we find that GC tissues and cell lines had higher A2aR levels than nontumor gastric tissues and cell lines. A2aR expression correlated positively with TNMstage, and associated with poor outcomes. Adenosine enhanced the expression of the stemness and epithelial–mesenchymal transition-associated genes by binding to A2aR. A2aR expression on GC cells promoted metastasis in vivo. The PI3K-AKT-mTOR signaling pathway was involved in adenosine-stimulated GC cell migration and invasion. Our results indicate that adenosine promotes GC cell invasion and metastasis by interacting with A2aR to enhance PI3K–AKT–mTOR pathway signaling.

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Section: Resultsmentioning

confidence: 95%

Adenosine interaction with adenosine receptor A2a promotes gastric cancer metastasis by enhancing PI3K–AKT–mTOR signaling

Shi

Miao

et al. 2019

MBoC

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“…It is well known that escape from apoptosis is the basis of cancer pathogenesis, and apoptosis drives cancer cells proliferate and metastasize [17]. Apoptosis involves a series of biochemical events, which are mediated by a variety of cellular signals [18]. On the one hand, Caspase3 is a major executioner caspase, active Caspase3 degrades multiple cellular proteins and is responsible for cell morphology changes and DNA fragmentation during apoptosis [19,20].…”

Section: Discussionmentioning

confidence: 99%

HSPA4 knockdown retarded progression and development of colorectal cancer

Zhang

Dai

et al. 2020

Preprint

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Background: Colorectal cancer (CRC) is the third most common cancer worldwide and the fourth most common cause of cancer death. The heat shock 70kDa protein 4 (HSPA4) participate in progression and development of cancers. However, the cellular functions, potential molecular mechanisms of HSPA4 in CRC are still largely unknown. Methods: In this study, qRT-PCR and Western Blot were used to identify the constructed HSPA4 knockdown cell lines, which was further used to construct mouse xenotransplantation models. Effects of HSPA4 knockdown on cell proliferation, apoptotic, cell cycle and migration of CRC were examined using Celigo cell counting assay, Flow cytometry, wound healing assay and Transwell assay, respectively. In addition, Human Apoptosis Antibody Array was performed to explore downstream molecular mechanism of HSPA4 in CRC cells. Results: HSPA4 was overexpressed in CRC, which was positively associated with lymphatic metastasis (N value), number of Lymph node. In addition, high expression of HSPA4 predicted poor prognosis of patients with CRC. Furthermore, HSPA4 knockdown inhibit proliferation, migration, promote apoptosis, and arrest cell cycle of CRC cells in vitro. Moreover, in vivo results supported HSPA4 knockdown inhibit tumor growth. Additionally, the induction of apoptosis of CRC cells by HSPA4 knockdown required the participation of a series of apoptosis-related proteins. The downregulation of HSPA4 promoted the progression of CRC cells, which resulted in alterations of PI3K/Akt, CCND1 and CDK6 in downstream signaling pathways. Conclusions: In sum, the downregulation of HSPA4 promoted CRC and may be a potential target for molecular therapy.

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“…The involvement of the four Ado receptors in apoptosis of cancer cells has been reported and reviewed recently [71,72]. Apoptosis can occur through A1 [73,74,75], A2A [76,77,78], A2B [79,80], and A3 [81,82,83,84,85,86,87,88,89] receptors (Figure 3).…”

Section: Adenosine Deaminasementioning

confidence: 94%

Purine-Metabolising Enzymes and Apoptosis in Cancer

Camici¹,

Garcia‐Gil

Pesi³

et al. 2019

Cancers

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The enzymes of both de novo and salvage pathways for purine nucleotide synthesis are regulated to meet the demand of nucleic acid precursors during proliferation. Among them, the salvage pathway enzymes seem to play the key role in replenishing the purine pool in dividing and tumour cells that require a greater amount of nucleotides. An imbalance in the purine pools is fundamental not only for preventing cell proliferation, but also, in many cases, to promote apoptosis. It is known that tumour cells harbour several mutations that might lead to defective apoptosis-inducing pathways, and this is probably at the basis of the initial expansion of the population of neoplastic cells. Therefore, knowledge of the molecular mechanisms that lead to apoptosis of tumoural cells is key to predicting the possible success of a drug treatment and planning more effective and focused therapies. In this review, we describe how the modulation of enzymes involved in purine metabolism in tumour cells may affect the apoptotic programme. The enzymes discussed are: ectosolic and cytosolic 5′-nucleotidases, purine nucleoside phosphorylase, adenosine deaminase, hypoxanthine-guanine phosphoribosyltransferase, and inosine-5′-monophosphate dehydrogenase, as well as recently described enzymes particularly expressed in tumour cells, such as deoxynucleoside triphosphate triphosphohydrolase and 7,8-dihydro-8-oxoguanine triphosphatase.

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Therapeutic potency of pharmacological adenosine receptors agonist/antagonist on cancer cell apoptosis in tumor microenvironment, current status, and perspectives

Cited by 26 publications

References 80 publications

Adenosine interaction with adenosine receptor A2a promotes gastric cancer metastasis by enhancing PI3K–AKT–mTOR signaling

Adenosine interaction with adenosine receptor A2a promotes gastric cancer metastasis by enhancing PI3K–AKT–mTOR signaling

HSPA4 knockdown retarded progression and development of colorectal cancer

Purine-Metabolising Enzymes and Apoptosis in Cancer

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