Mutant p53R248Qdownregulates oxidative phosphorylation and upregulates glycolysis under normoxia and hypoxia in human cervix cancer cells

2018 ◽  
Vol 234 (5) ◽  
pp. 5524-5536 ◽  
Author(s):  
Ileana Hernández-Reséndiz ◽  
Juan Carlos Gallardo-Pérez ◽  
Ambar López-Macay ◽  
Diana Xochiquetzal Robledo-Cadena ◽  
Enrique García-Villa ◽  
...  
Keyword(s):  
Oxidative Phosphorylation ◽  
Cancer Cells ◽  
Cervix Cancer ◽  
Human Cervix

scholarly journals Non-Steroidal Anti-Inflammatory Drugs Increase Cisplatin, Paclitaxel, and Doxorubicin Efficacy against Human Cervix Cancer Cells

2020 ◽  
Vol 13 (12) ◽  
pp. 463
Author(s):  
Diana Xochiquetzal Robledo-Cadena ◽  
Juan Carlos Gallardo-Pérez ◽  
Víctor Dávila-Borja ◽  
Silvia Cecilia Pacheco-Velázquez ◽  
Javier Alejandro Belmont-Díaz ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cell Cultures ◽  
Therapeutic Index ◽  
Inhibitory Effect ◽  
Cervix Cancer ◽  
3T3 Fibroblasts ◽  
U373 Cell ◽  
Ic50 Values ◽  
Anti Inflammatory ◽  
Human Cervix

This study shows that the non-steroidal anti-inflammatory drug (NSAID) celecoxib and its non-cyclooxygenase-2 (COX2) analogue dimethylcelecoxib (DMC) exert a potent inhibitory effect on the growth of human cervix HeLa multi-cellular tumor spheroids (MCTS) when added either at the beginning (“preventive protocol”; IC50 = 1 ± 0.3 nM for celecoxib and 10 ± 2 nM for DMC) or after spheroid formation (“curative protocol”; IC50 = 7.5 ± 2 µM for celecoxib and 32 ± 10 µM for DMC). These NSAID IC50 values were significantly lower than those attained in bidimensional HeLa cells (IC50 = 55 ± 9 µM celecoxib and 48 ± 2 µM DMC) and bidimensional non-cancer cell cultures (3T3 fibroblasts and MCF-10A mammary gland cells with IC50 from 69 to >100 µM, after 24 h). The copper-based drug casiopeina II-gly showed similar potency against HeLa MCTS. Synergism analysis showed that celecoxib, DMC, and casiopeinaII-gly at sub-IC50 doses increased the potency of cisplatin, paclitaxel, and doxorubicin to hinder HeLa cell proliferation through a significant abolishment of oxidative phosphorylation in bidimensional cultures, with no apparent effect on non-cancer cells (therapeutic index >3.6). Similar results were attained with bidimensional human cervix cancer SiHa and human glioblastoma U373 cell cultures. In HeLa MCTS, celecoxib, DMC and casiopeina II-gly increased cisplatin toxicity by 41–85%. These observations indicated that celecoxib and DMC used as adjuvant therapy in combination with canonical anti-cancer drugs may provide more effective alternatives for cancer treatment.

scholarly journals Primula vulgaris extract induces cell cycle arrest and apoptosis in human cervix cancer cells

2018 ◽  
Vol 8 (5) ◽  
pp. 307-311 ◽  
Author(s):  
Selim Demir ◽  
Ibrahim Turan ◽  
Rezzan Aliyazicioglu ◽  
Serap Ozer Yaman ◽  
Yuksel Aliyazicioglu
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Cervix Cancer ◽  
Cycle Arrest ◽  
Primula Vulgaris ◽  
Human Cervix

PKCε is essential for gelsolin expression by histone deacetylase inhibitor apicidin in human cervix cancer cells

2007 ◽  
Vol 354 (3) ◽  
pp. 769-775 ◽  
Author(s):  
Dae-Wook Eun ◽  
Seong Hoon Ahn ◽  
Jeong Soo You ◽  
Jong Woo Park ◽  
Eun Kyung Lee ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Histone Deacetylase ◽  
Histone Deacetylase Inhibitor ◽  
Cervix Cancer ◽  
Deacetylase Inhibitor ◽  
Human Cervix

Water Soluble C 60 -Liposome and the Biological Effect of C 60 to Human Cervix Cancer Cells

1994 ◽  
Vol 11 (4) ◽  
pp. 207-210 ◽  
Author(s):  
Wenzhu Li (Wenzhou Li) ◽  
Kaixian Qian ◽  
Wendong Huang ◽  
Xinxin Zhang ◽  
Wanxi Chen
Keyword(s):  
Cancer Cells ◽  
Biological Effect ◽  
Water Soluble ◽  
Cervix Cancer ◽  
Soluble C ◽  
Water Soluble C ◽  
Human Cervix

COX-1 is coupled with mPGES-1 and ABCC4 in human cervix cancer cells

2009 ◽  
Vol 330 (1-2) ◽  
pp. 131-140 ◽  
Author(s):  
Hana Radilova ◽  
Antonin Libra ◽  
Sarka Holasova ◽  
Martina Safarova ◽  
Alena Viskova ◽  
...  
Keyword(s):  
Cancer Cells ◽  
Cervix Cancer ◽  
Cox 1 ◽  
Human Cervix

scholarly journals TAMI-57. MEDULLOBLASTOMA UTILIZE GABA TRANSAMINASE TO SURVIVE IN THE CEREBROSPINAL FLUID MICROENVIRONMENT AND PROMOTE LEPTOMENINGEAL DISSEMINATION

2020 ◽  
Vol 22 (Supplement_2) ◽  
pp. ii225-ii226
Author(s):  
Vahan Martirosian ◽  
Krutika Deshpande ◽  
Hao Zhou ◽  
Keyue Shen ◽  
Vazgen Stepanosyan ◽  
...  
Keyword(s):  
Energy Source ◽  
Cerebrospinal Fluid ◽  
Oxidative Phosphorylation ◽  
Cancer Cells ◽  
Metastatic Cancer ◽  
Leptomeningeal Metastases ◽  
Metabolic Phenotype ◽  
Leptomeningeal Disease ◽  
Neural Cells ◽  
Gaba Transaminase

Abstract Medulloblastoma (MB) is a malignant pediatric brain tumor. Studies have shown heterogeneous cells amongst the tumor bulk which mirror normal neural cells in various neurodevelopmental stages. To discern exploited mechanisms promoting MB leptomeningeal disease, we drew conclusions from developmental neurobiology. In normal differentiation, the metabolic phenotype in proliferating neural progenitor cells evolves from a glycolysis-dependent to an oxidative phosphorylation-reliant energetic profile in quiescent differentiated neurons. Cancer cells mirror this evolution, which also grants them the capability to utilize alternative nutrients in the microenvironment as an energy source. Considering metastatic cells are typically in a dormant state and primarily utilize oxidative phosphorylation, we hypothesized metastatic MB cells emulate a quiescent neuron-like cellular profile to survive in the cerebrospinal fluid and form leptomeningeal metastases. To examine this, we query the expression of GABA catabolic enzyme GABA transaminase (ABAT) in MB. GABA is found in the cerebellar and leptomeningeal microenvironments, and is utilized by metastatic cancer cells in the CNS as an energy source. We correlate an increase in ABAT expression with neurodevelopment and show heterogeneous expression of this protein in primary MB tumors. MB cells with increased expression of ABAT were slower-dividing, expressed a genetic and metabolic phenotype reminiscent of quiescent neuron-like cells, and had increased capability to metabolize GABA. Conversely, lower expression of ABAT was associated with an increased proliferation rate and correlated with a progenitor-like cellular profile. Transplantation of MB cells into the leptomeningeal compartment decreased proliferative capacity and enhanced ABAT expression. Xenograft models showed MB cells with ABAT knockdown had increased growth in the cerebellar microenvironment. Conversely, MB cells with ABAT overexpression transplanted into the cerebrospinal fluid formed leptomeningeal metastases whereas ABAT knockdown cells could not. These results suggest ABAT expression in MB cells can be modulated by the tumor microenvironment and is required to form leptomeningeal metastases.

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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