scholarly journals Docosahexaenoic acid alters cell death, cancer and cell‐cycle signaling networks in breast cancer cell lines

2012 ◽  
Vol 26 (S1) ◽  
Author(s):  
Catherine J Field ◽  
Julia B Ewaschuk ◽  
Randy Nelson ◽  
Marnie Newell ◽  
Rene Jacobs
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Docosahexaenoic Acid ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Signaling Networks ◽  
Breast Cancer Cell Lines ◽  
Cell Cycle Signaling

Abstract 4463: Riluzole effectively modulates cell cycle and cell death in a molecularly diverse set of breast cancer cell lines

2015 ◽  
Author(s):  
Sonia C. Dolfi ◽  
Daniel J. Medina ◽  
Shridar Ganesan ◽  
Alexei Vazquez ◽  
Kim M. Hirshfield
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Death ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Cell Lines ◽  
Breast Cancer Cell Lines

scholarly journals A chemical screen in diverse breast cancer cell lines reveals genetic enhancers and suppressors of sensitivity to PI3K isoform-selective inhibition

2008 ◽  
Vol 415 (1) ◽  
pp. 97-110 ◽  
Author(s):  
Neil E. Torbett ◽  
Antonio Luna-Moran ◽  
Zachary A. Knight ◽  
Andrew Houk ◽  
Mark Moasser ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Cycle ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Cancer Therapeutics ◽  
Cancer Cell Lines ◽  
Genetic Alterations ◽  
Breast Cancer Cell Lines ◽  
Selective Inhibitors

The PI3K (phosphoinositide 3-kinase) pathway regulates cell proliferation, survival and migration and is consequently of great interest for targeted cancer therapy. Using a panel of small-molecule PI3K isoform-selective inhibitors in a diverse set of breast cancer cell lines, we have demonstrated that the biochemical and biological responses were highly variable and dependent on the genetic alterations present. p110α inhibitors were generally effective in inhibiting the phosphorylation of PKB (protein kinase B)/Akt and S6, two downstream components of PI3K signalling, in most cell lines examined. In contrast, p110β-selective inhibitors only reduced PKB/Akt phosphorylation in PTEN (phosphatase and tensin homologue deleted on chromosome 10) mutant cell lines, and was associated with a lesser decrease in S6 phosphorylation. PI3K inhibitors reduced cell viability by causing cell-cycle arrest in the G1 phase, with multi-targeted inhibitors causing the most potent effects. Cells expressing mutant Ras were resistant to the cell-cycle effects of PI3K inhibition, which could be reversed using inhibitors of Ras signalling pathways. Taken together, our data indicate that these compounds, alone or in suitable combinations, may be useful as breast cancer therapeutics, when used in appropriate genetic contexts.

scholarly journals AKT but not MYC promotes reactive oxygen species-mediated cell death in oxidative culture

2019 ◽  
Author(s):  
Dongqing Zheng ◽  
Jonathan H. Sussman ◽  
Matthew P. Jeon ◽  
Sydney T. Parrish ◽  
Alireza Delfarah ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Reactive Oxygen Species ◽  
Cell Death ◽  
Oxidative Phosphorylation ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Cell ◽  
Breast Cancer Cell ◽  
Breast Cancer Cell Lines ◽  
Oxygen Species

ABSTRACTOncogenes can generate metabolic vulnerabilities in cancer cells. Here, we tested how AKT and MYC affect the ability of cells to shift between respiration and glycolysis. Using immortalized mammary epithelial cells, we discovered that constitutively active AKT but not MYC induced cell death in galactose culture, where cells must rely on oxidative phosphorylation for energy generation. However, the negative effects of AKT were short-lived, and AKT-expressing cells recommenced growth after ~15 days in galactose. To identify the mechanisms regulating AKT-mediated cell death, we used metabolomics and found that AKT cells dying in galactose upregulated glutathione metabolism. Next, using proteomics, we discovered that AKT-expressing cells dying in galactose upregulated nonsense-mediated mRNA decay, a marker of sensitivity to oxidative stress. We therefore measured levels of reactive oxygen species (ROS) and discovered that galactose induced ROS in cells expressing AKT but not MYC. Additionally, ROS were required for the galactose-induced death of AKT-expressing cells. We then tested whether these findings could be replicated in breast cancer cell lines with constitutively active AKT signaling. Indeed, we found that galactose induced rapid cell death in breast cancer cell lines and that ROS were required for galactose-induced cell death. Together, our results demonstrate that AKT but not MYC induces a metabolic vulnerability in cancer cells, namely the restricted flexibility to use oxidative phosphorylation.ImplicationsThe discovery that AKT but not MYC restricts the ability to utilize oxidative phosphorylation highlights that therapeutics targeting tumor metabolism must be tailored to the individual genetic profile of tumors.

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