Targeting E2F Sensitizes Prostate Cancer Cells to Drug-Induced Replication Stress by Promoting Unscheduled CDK1 Activity DOI Open Access
M. El Hamidi, Ainhoa Eriz,

Jone Mitxelena

et al.

Cancers, Journal Year: 2022, Volume and Issue: 14(19), P. 4952 - 4952

Published: Oct. 10, 2022

E2F1/E2F2 expression correlates with malignancy in prostate cancer (PCa), but its functional significance remains unresolved. To define the mechanisms governed by E2F PCa, we analyzed contribution of target genes to control genome integrity, and impact modulating activity on PCa progression. We show that silencing or inhibiting induces DNA damage during S phase potentiates 5-FU-induced replication stress cellular toxicity. Inhibition downregulates targets involved nucleotide biosynthesis (TK1, DCK, TYMS), whose is upregulated 5-FU. However, their enzymatic products failed rescue knockdown cells, suggesting additional for function. Interestingly, targeting cells reduced WEE1 resulted premature CDK1 activation phase. CDK1/CDK2 prevented induced loss, safeguard integrity restraining activity. Importantly, combined inhibition ATR boosted dramatically tumorigenic capacity xenografts. Collectively, combination drugs repair a promising strategy provoke catastrophic levels could be applied treatment.

Language: Английский

Active biomonitoring of stream ecosystems: untargeted metabolomic and proteomic responses and free radical scavenging activities in mussels DOI

Muhammad Rivaldi,

Andri Frediansyah,

Solihatun Amidan Amatul Aziz

et al.

Ecotoxicology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 9, 2025

Language: Английский

Citations

0
Combating chemoresistance: Current approaches & nanocarrier mediated targeted delivery DOI
Siuli Shaw, Subrata K. Pore,

D.-M. Liu

et al.

Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Journal Year: 2025, Volume and Issue: unknown, P. 189261 - 189261

Published: Jan. 1, 2025

Language: Английский

Citations

0
Identification of pyrimidine metabolism-based molecular subtypes and prognostic signature to predict immune landscape and guide clinical treatment in prostate cancer DOI Creative Commons

Yu‐Zhong Yu,

Xiao Xie,

Maoping Cai

et al.

Annals of Medicine, Journal Year: 2025, Volume and Issue: 57(1)

Published: Jan. 13, 2025

Background We previously described the enrichment of plasma exosome metabolites in CRPC, PCa, and TFC cohorts, found significant differences pyrimidine metabolites. The PMGs is associated with clinical prognosis several cancers, but its biological role PCa still unclear.

Language: Английский

Citations

0
Vaccinia growth factor-dependent modulation of the mTORC1-CAD axis upon nutrient restriction DOI Creative Commons
Lara Dsouza,

Anil Pant,

Blake Pope

et al.

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 16, 2025

The molecular mechanisms by which vaccinia virus (VACV), the prototypical member of poxviridae family, reprograms host cell metabolism remain largely unexplored. Additionally, cells sense and respond to fluctuating nutrient availability, thereby modulating metabolic pathways ensure cellular homeostasis. Understanding how VACV modulates in response signals is crucial for understanding viral replication mechanisms, with potential developing antiviral therapies. In this study, we establish importance de novo pyrimidine synthesis during infection. We report significance growth factor (VGF), a early protein homolog epidermal (EGF), enabling phosphorylate key enzyme CAD pathway at serine 1859, site known positively regulate activity. Although nutrient-poor conditions typically inhibit mTORC1 activation, activates via mTORC1-S6K1 signaling axis VGF-dependent manner, especially upon glutamine asparagine limitation. However, unlike its EGF, VGF peptide alone, absence infection, has minimal ability activate CAD. This suggests involvement other factors yet be identified. Our research provides foundation regulation significant pathway, shedding new light on under distinct nutritional environments. study not only contribute advancement treatments but also improve development as an oncolytic agent vaccine vector.IMPORTANCEViruses often reprogram facilitate replication. How poxviruses, such prototype member, modulate well understood. affects these learning about treatments. highlights found that similar helps pathway. Upon limitation, needed activation through mTORC1-S6K signaling. alone unable independent suggesting factor(s). sheds regulates holds promise improving cancer treatment vaccine.

Language: Английский

Citations

0
A critical review on purine and pyrimidine heterocyclic derivatives and their designed molecules in Cancer DOI Creative Commons

Gajanana Sanglikar,

Anand KumarTengli

Results in Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 102210 - 102210

Published: March 1, 2025

Language: Английский

Citations

0
Histology-resolved proteomics reveals distinct tumor and stromal profiles in low- and high-grade prostate cancer DOI Creative Commons
Allison L. Hunt, Waleed Barakat, Sasha C. Makohon‐Moore

et al.

Clinical Proteomics, Journal Year: 2025, Volume and Issue: 22(1)

Published: April 20, 2025

Language: Английский

Citations

0
Metabolic Pathway Analysis of Tumors Using Stable Isotopes DOI

Qiufen Bi,

Junzhang Zhao,

Jun Nie

et al.

Seminars in Cancer Biology, Journal Year: 2025, Volume and Issue: 113, P. 9 - 24

Published: May 9, 2025

Language: Английский

Citations

0
Effects of metabolic cancer therapy on tumor microenvironment DOI Creative Commons
Petra Hyroššová,

Mirko Milošević,

Josef Škoda

et al.

Frontiers in Oncology, Journal Year: 2022, Volume and Issue: 12

Published: Dec. 13, 2022

Targeting tumor metabolism for cancer therapy is an old strategy. In fact, historically the first effective therapeutics were directed at nucleotide metabolism. The spectrum of metabolic drugs considered in increases rapidly – clinical trials are progress agents glycolysis, oxidative phosphorylation, glutaminolysis and several others. These pathways essential cell proliferation redox homeostasis, but also required, to various degrees, other types present microenvironment, including immune cells, endothelial cells fibroblasts. How metabolism-targeted treatments impact these tumor-associated not fully understood, even though their response may co-determine overall effectivity therapy. Indeed, dependencies stromal have been overlooked a long time. Therefore, it important that context as understanding vulnerabilities both can guide new treatment concepts help better understand resistance. this review we discuss recent findings covering interventions on cellular components microenvironment implications

Language: Английский

Citations

13
Diverse Pharmacological Potential of Various Substituted Pyrimidine Derivatives DOI
Abdulaziz Alsharif, Mamdouh Allahyani, Mohammed Al Mohaini

et al.

Current Organic Chemistry, Journal Year: 2023, Volume and Issue: 27(20), P. 1779 - 1798

Published: Nov. 1, 2023

Abstract: In many significant bioactive heterocyclic compounds, the six-membered ring pyrimidines play a major role as components. There is lot of room for innovation in fields medicinal chemistry and chemical industries because numerous pyrimidine synthesis methods their varied reactions. The pharmacological effects derivatives include anticonvulsant, antibacterial, antifungal, antiviral, antitubercular, anticancer, antimicrobial, antihypertensive, antiulcer, anti-inflammatory, antimalarial, antioxidant, analgesic, sedative, anti-depressive, antipyretic properties, etc. synthetic adaptability has made it possible to create wide range structurally different analogs, including analogs from substitution on at various places, which aided design variety therapeutic targets. This review's goal examine derivatives. review provides an overview compounds biological activities examines novel molecules containing rings future.

Language: Английский

Citations

7
Reprogramming of pyrimidine nucleotide metabolism supports vigorous cell proliferation of normal and malignant T cells DOI Creative Commons
Tatsuro Watanabe, Yuta Yamamoto, Yuki Kurahashi

et al.

Blood Advances, Journal Year: 2024, Volume and Issue: 8(6), P. 1345 - 1358

Published: Jan. 8, 2024

Abstract Adult T-cell leukemia/lymphoma (ATL) is triggered by infection with human lymphotropic virus-1 (HTLV-1). Here, we describe the reprogramming of pyrimidine biosynthesis in both normal T cells and ATL through regulation uridine-cytidine kinase 2 (UCK2), which supports vigorous proliferation. UCK2 catalyzes monophosphorylation cytidine/uridine their analogues during drug metabolism. We found that was overexpressed aberrantly HTLV-1–infected but not cells. activation via receptor (TCR) signaling induced expression Somatic alterations epigenetic modifications activate TCR signaling. Therefore, believe dysregulated Recently, established azacitidine-resistant (AZA-R) showing absent UCK2. AZA-R proliferated normally vitro, whereas knockdown inhibited cell growth. Although uridine cytidine accumulated cells, possibly because dysfunction salvage loss expression, amount UTP CTP almost same as parental Furthermore, were more susceptible to an inhibitor dihydroorotic acid dehydrogenase, performs rate-limiting enzyme de novo nucleotide biosynthesis, resistant dipyridamole, suggesting adapt increasing biosynthesis. Taken together, data suggest fine-tuning proliferation

Language: Английский

Citations

2