2‑Cl‑IB‑MECA regulates the proliferative and drug resistance pathways, and facilitates chemosensitivity in pancreatic and liver cancer cell lines

Kotulová, Jana; Lonova, Katerina; Kubíčková, Agáta; Vrbková, Jana; Kouřilová, Pavla; Hajdúch, Marián; Džubák, Petr

doi:10.3892/ijmm.2022.5086

Cited by 2 publications

(2 citation statements)

References 90 publications

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“…Our in vitro and in vivo findings are consistent with former studies investigating namodenoson in liver cancer, in which A3AR-mediated growth inhibition was observed and the mechanism-of-action was shown to involve the NF-κB as well as the Wnt pathways and apoptosis induction [13][14][15]. The mechanism of action described in the present work is also aligned with former studies demonstrating anti-tumor effects in melanoma, colon, prostate, lung, and thyroid carcinoma, as well as lymphoma.…”

Section: Discussionsupporting

confidence: 90%

Namodenoson Inhibits the Growth of Pancreatic Carcinoma via Deregulation of the Wnt/β-catenin, NF-κB, and RAS Signaling Pathways

Itzhak,

Bareket-Samish,

Fishman

2023

Biomolecules

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Namodenoson, an A3 adenosine receptor (A3AR) agonist, is currently being used in a phase III trial in advanced liver cancer. We examined the anti-growth effect of namodenoson on pancreatic carcinoma cells and investigated the molecular mechanism involved. BxPC-3 pancreatic carcinoma cells were cultured with namodenoson (5–20 nM for 24 h at 37 °C), and the Presto Blue assay was used to monitor cell growth. Western blot analyses were performed on BxPC-3 cells (20 nM namodenoson for 24 h at 37 °C) to evaluate the expression levels of cell growth regulatory proteins. In vivo studies involved the subcutaneous inoculation of BxPC-3 cells into nude mice, randomizing the mice into namodenoson (10 μg/kg twice daily for 35 days) vs. control, and monitoring tumor size twice weekly. Treatment with namodenoson was associated with the significant dose-dependent inhibition of BxPC-3 cell growth, which was mitigated by the A3AR antagonist MRS1523. Western blot analyses showed that namodenoson treatment modulated the expression of NF-κB, as well as proteins in the Wnt/β-catenin and the RAS signaling pathways, leading to the upregulation of apoptotic proteins (Bad, Bax). In vivo studies also showed the significant inhibition of pancreatic carcinoma tumor growth with namodenoson. In conclusion, our findings support the continued development of namodenoson as a treatment for pancreatic cancer.

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Section: Discussionsupporting

confidence: 90%

Namodenoson Inhibits the Growth of Pancreatic Carcinoma via Deregulation of the Wnt/β-catenin, NF-κB, and RAS Signaling Pathways

Itzhak,

Bareket-Samish,

Fishman

2023

Biomolecules

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“…This dual role adds a further level of complexity to how c-Myc contributes to tumourigenesis. Under certain conditions, c-Myc can promote cell survival by upregulating anti-apoptotic genes, which can block pro-apoptotic signals in cancer cells [15]. However, c-Myc can also induce apoptosis when required to safeguard against the uncontrolled proliferation of damaged cells.…”

Section: Introductionmentioning

confidence: 99%

Isoform-Directed Control of c-Myc Functions: Understanding the Balance from Proliferation to Growth Arrest

Kubickova,

De Sanctis,

Hajduch

2023

IJMS

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The transcription factor c-Myc, a key regulator of cellular processes, has long been associated with roles in cell proliferation and apoptosis. This review analyses the multiple functions of c-Myc by examining the different c-Myc isoforms in detail. The impact of different c-Myc isoforms, in particular p64 and p67, on fundamental biological processes remains controversial. It is necessary to investigate the different isoforms in the context of proto-oncogenesis. The current knowledge base suggests that neoplastic lesions may possess the means for self-destruction via increased c-Myc activity. This review presents the most relevant information on the c-Myc locus and focuses on a number of isoforms, including p64 and p67. This compilation provides a basis for the development of therapeutic approaches that target the potent growth arresting and pro-apoptotic functions of c-Myc. This information can then be used to develop targeted interventions against specific isoforms with the aim of shifting the oncogenic effects of c-Myc from pro-proliferative to pro-apoptotic. The research summarised in this review can deepen our understanding of how c-Myc activity contributes to different cellular responses, which will be crucial in developing effective therapeutic strategies; for example, isoform-specific approaches may allow for precise modulation of c-Myc function.

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2‑Cl‑IB‑MECA regulates the proliferative and drug resistance pathways, and facilitates chemosensitivity in pancreatic and liver cancer cell lines

Cited by 2 publications

References 90 publications

Namodenoson Inhibits the Growth of Pancreatic Carcinoma via Deregulation of the Wnt/β-catenin, NF-κB, and RAS Signaling Pathways

Namodenoson Inhibits the Growth of Pancreatic Carcinoma via Deregulation of the Wnt/β-catenin, NF-κB, and RAS Signaling Pathways

Isoform-Directed Control of c-Myc Functions: Understanding the Balance from Proliferation to Growth Arrest

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