A novel small-molecule fatty acid synthase inhibitor with antitumor activity by cell cycle arrest and cell division inhibition

2021 ◽  
pp. 113407
Author(s):  
Hongyan Qu ◽  
Kai Shan ◽  
Chunlei Tang ◽  
Guozhen Cui ◽  
Guoling Fu ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Fatty Acid ◽  
Cell Division ◽  
Antitumor Activity ◽  
Cell Cycle Arrest ◽  
Small Molecule ◽  
Fatty Acid Synthase ◽  
Cycle Arrest ◽  
Synthase Inhibitor ◽  
Cell Division Inhibition

scholarly journals A Fatty Acid Synthase Blockade Induces Tumor Cell-cycle Arrest by Down-regulating Skp2

2004 ◽  
Vol 279 (29) ◽  
pp. 30540-30545 ◽  
Author(s):  
Lynn M. Knowles ◽  
Fumiko Axelrod ◽  
Cecille D. Browne ◽  
Jeffrey W. Smith
Keyword(s):  
Cell Cycle ◽  
Fatty Acid ◽  
Tumor Cell ◽  
Cell Cycle Arrest ◽  
Fatty Acid Synthase ◽  
Cycle Arrest

scholarly journals Anticancer potential of nitric oxide (NO) in neuroblastoma treatment

RSC Advances ◽  
2021 ◽  
Vol 11 (16) ◽  
pp. 9112-9120
Author(s):  
Jenna L. Gordon ◽  
Kristin J. Hinsen ◽  
Melissa M. Reynolds ◽  
Tyler A. Smith ◽  
Haley O. Tucker ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cell Cycle ◽  
Cell Division ◽  
Cell Viability ◽  
Cell Cycle Arrest ◽  
Neuroblastoma Cells ◽  
Cycle Arrest

S-Nitrosoglutathione (GSNO) reduces cell viability, inhibits cell division, and induces cell cycle arrest and apoptosis in neuroblastoma cells.

Novel small molecule inhibitor of Kpnβ1 induces cell cycle arrest and apoptosis in cancer cells

2021 ◽  
pp. 112637
Author(s):  
Aderonke Ajayi-Smith ◽  
Pauline van der Watt ◽  
Nonkululeko Mkwanazi ◽  
Sarah Carden ◽  
John O. Trent ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Cycle Arrest ◽  
Molecule Inhibitor ◽  
Apoptosis In Cancer Cells

scholarly journals Mutant p53L194F Harboring Luminal-A Breast Cancer Cells Are Refractory to Apoptosis and Cell Cycle Arrest in Response to MortaparibPlus, a Multimodal Small Molecule Inhibitor

Cancers ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 3043
Author(s):  
Ahmed Elwakeel ◽  
Anissa Nofita Sari ◽  
Jaspreet Kaur Dhanjal ◽  
Hazna Noor Meidinna ◽  
Durai Sundar ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Small Molecule ◽  
Breast Cancer Cells ◽  
Luminal A ◽  
Molecular Analyses ◽  
Cycle Arrest ◽  
Mcf 7

We previously performed a drug screening to identify a potential inhibitor of mortalin–p53 interaction. In four rounds of screenings based on the shift in mortalin immunostaining pattern from perinuclear to pan-cytoplasmic and nuclear enrichment of p53, we had identified MortaparibPlus (4-[(1E)-2-(2-phenylindol-3-yl)-1-azavinyl]-1,2,4-triazole) as a novel synthetic small molecule. In order to validate its activity and mechanism of action, we recruited Luminal-A breast cancer cells, MCF-7 (p53wild type) and T47D (p53L194F) and performed extensive biochemical and immunocytochemical analyses. Molecular analyses revealed that MortaparibPlus is capable of abrogating mortalin–p53 interaction in both MCF-7 and T47D cells. Intriguingly, upregulation of transcriptional activation function of p53 (as marked by upregulation of the p53 effector gene—p21WAF1—responsible for cell cycle arrest and apoptosis) was recorded only in MortaparibPlus-treated MCF-7 cells. On the other hand, MortaparibPlus-treated T47D cells exhibited hyperactivation of PARP1 (accumulation of PAR polymer and decrease in ATP levels) as a possible non-p53 tumor suppression program. However, these cells did not show full signs of either apoptosis or PAR-Thanatos. Molecular analyses attributed such a response to the inability of MortaparibPlus to disrupt the AIF–mortalin complexes; hence, AIF did not translocate to the nucleus to induce chromatinolysis and DNA degradation. These data suggested that the cancer cells possessing enriched levels of such complexes may not respond to MortaparibPlus. Taken together, we report the multimodal anticancer potential of MortaparibPlus that warrants further attention in laboratory and clinical studies.

scholarly journals Copper-Binding Small Molecule Induces Oxidative Stress and Cell-Cycle Arrest in Glioblastoma-Patient-Derived Cells

2018 ◽  
Vol 25 (5) ◽  
pp. 585-594.e7 ◽  
Author(s):  
Kenichi Shimada ◽  
Eduard Reznik ◽  
Michael E. Stokes ◽  
Lakshmi Krishnamoorthy ◽  
Pieter H. Bos ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Small Molecule ◽  
Copper Binding ◽  
Glioblastoma Patient ◽  
Cycle Arrest

scholarly journals Fatty acid oxidation inhibitor etomoxir suppresses tumor progression and induces cell cycle arrest via PPARγ-mediated pathway in bladder cancer

2019 ◽  
Vol 133 (15) ◽  
pp. 1745-1758 ◽  
Author(s):  
Songtao Cheng ◽  
Gang Wang ◽  
Yejinpeng Wang ◽  
Liwei Cai ◽  
Kaiyu Qian ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Fatty Acid ◽  
Tumor Progression ◽  
Cell Cycle Arrest ◽  
Fatty Acid Oxidation ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Acid Oxidation ◽  
Cycle Arrest

Abstract Tumor cells rely on aerobic glycolysis as their main energy resource (Warburg effect). Recent research has highlighted the importance of lipid metabolism in tumor progression, and certain cancers even turn to fatty acids as the main fuel. Related studies have identified alterations of fatty acid metabolism in human bladder cancer (BCa). Our microarray analysis showed that fatty acid metabolism was activated in BCa compared with normal bladder. The free fatty acid (FFA) level was also increased in BCa compared with paracancerous tissues. Inhibition of fatty acid oxidation (FAO) with etomoxir caused lipid accumulation, decreased adenosine triphosphate (ATP) and nicotinamide adenine dinucleotide phosphate (NADPH) levels, suppressed BCa cell growth in vitro and in vivo, and reduced motility of BCa cells via affecting epithelial–mesenchymal transition (EMT)-related proteins. Furthermore, etomoxir induced BCa cell cycle arrest at G0/G1 phase through peroxisome proliferator-activated receptor (PPAR) γ-mediated pathway with alterations in fatty acid metabolism associated gene expression. The cell cycle arrest could be reversed by PPARγ antagonist GW9662. Taken together, our results suggest that inhibition of FAO with etomoxir may provide a novel avenue to investigate new therapeutic approaches to human BCa.

Induction of cell-cycle arrest and apoptosis in glioblastoma stem-like cells by WP1193, a novel small molecule inhibitor of the JAK2/STAT3 pathway

2012 ◽  
Vol 107 (3) ◽  
pp. 487-501 ◽  
Author(s):  
Ke Sai ◽  
Shuzhen Wang ◽  
Veerakumar Balasubramaniyan ◽  
Charles Conrad ◽  
Frederick F. Lang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Small Molecule ◽  
Small Molecule Inhibitor ◽  
Stat3 Pathway ◽  
Cycle Arrest ◽  
Molecule Inhibitor

scholarly journals Delivery of a TNF‐α–derived peptide by nanoparticles enhances its antitumor activity by inducing cell‐cycle arrest and caspase‐dependent apoptosis

2018 ◽  
Vol 32 (12) ◽  
pp. 6948-6964 ◽  
Author(s):  
Qiuxia Yan ◽  
Xueming Chen ◽  
Huizhen Gong ◽  
Pei Qiu ◽  
Xing Xiao ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Antitumor Activity ◽  
Cell Cycle Arrest ◽  
Cycle Arrest ◽  
Tnf Α
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