scholarly journals Kinetic analysis of lipid metabolism in live breast cancer cells via nonlinear optical microscopy

2021 ◽  
Author(s):  
Nellone Reid ◽  
Jue Hou ◽  
Eric Potma ◽  
Bruce J. Tromberg
Keyword(s):  
Breast Cancer ◽  
Lipid Metabolism ◽  
Kinetic Analysis ◽  
Optical Microscopy ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Nonlinear Optical ◽  
Nonlinear Optical Microscopy

scholarly journals Kinetic Analysis of Lipid Metabolism in Live Breast Cancer Cells via Nonlinear Optical Microscopy

2019 ◽  
Author(s):  
J. Hou ◽  
N. E. Reid ◽  
B. J. Tromberg ◽  
E. O. Potma
Keyword(s):  
Breast Cancer ◽  
Lipid Metabolism ◽  
Optical Microscopy ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
De Novo ◽  
Lipid Synthesis ◽  
Acid Synthesis ◽  
Live Cells ◽  
Consumption Rates

AbstractInvestigating the behavior of breast cancer cells via reaction kinetics may help unravel the mechanisms that underlie metabolic changes in tumors. However, obtaining human in vivo kinetic data is challenging due to difficulties associated with measuring these parameters. Non-destructive methods of measuring lipid content in live cells, provide a novel approach to quantitatively model lipid synthesis and consumption. In this study, two-photon excited fluorescence (TPEF) was used to determine metabolic rates via the cell’s optical redox ratio (ORR) as reported by fluorescence intensity ratios of metabolic coenzymes, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FAD+). Concurrently, coherent Raman scattering (CRS) microscopy was used to probe de novo intracellular lipid content. Combining non-linear optical microscopy and Michaelis-Menten-kinetics based simulations, we isolated fatty acid synthesis/consumption rates and elucidated effects of altered lipid metabolism in T47D breast cancer cells. When treated with 17β-Estradiol (E2), cancer cells showed a 3-fold increase in beta-oxidation rate as well as a 50% increase in cell proliferation rate. Similarly, the rate of de novo lipid synthesis in cancer cells treated with E2 was increased by 60%. Furthermore, we treated T47D cells with etomoxir (ETO) and observed that cancer cells treated with ETO exhibited a ∼70% reduction in β-oxidation. These results show the ability to probe lipid alterations in live cells with minimum interruption, to characterize both glucose and lipid metabolism in breast cancer cells via quantitative kinetic models and parameters.Statement of SignificanceCombining non-linear optical microscopy (NLOM) and deuterium labeling provides insight into lipid metabolism in live cancer cells during cancer development and progression. The dynamic metabolic data is modelled with Michaelis-Menten-kinetics to independently quantify the lipid synthesis and utilization in cancer cells. Changes in lipid levels are found to originate from de novo lipid synthesis using glucose as a source, lipid consumption from β-oxidation and lipid consumption from cell proliferation, processes that can separately analyzed with the Michaelis-Menten model. In this work, we isolate fatty acid synthesis/consumption rates and elucidated effects of altered lipid metabolism in T47D breast cancer cells in response to estradiol stimulation and etomoxir treatment, dynamic processes that cannot be easily observed without the application of appropriate models.

Abstract 3744: Differences in lipid metabolism between non-metastatic and metastatic breast cancer cells

2020 ◽  
Author(s):  
Chaylen Andolino ◽  
Josie Asher ◽  
Alyssa S. Zembroski ◽  
Kimberly Buhman ◽  
Dorothy Teegarden
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Lipid Metabolism ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Metastatic Breast

Oncogene-mediated changes in lipid metabolism in breast cancer cells

2009 ◽  
Vol 160 ◽  
pp. S35
Author(s):  
Cristina Cadenas ◽  
Alice Langer ◽  
Eva-Maria Hein ◽  
Heiko Hayen ◽  
Matthias Hermes ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lipid Metabolism ◽  
Cancer Cells ◽  
Breast Cancer Cells

scholarly journals Adiponectin triggers breast cancer cell death via fatty acid metabolic reprogramming

2022 ◽  
Vol 41 (1) ◽  
Author(s):  
Duc-Vinh Pham ◽  
Pil-Hoon Park
Keyword(s):  
Breast Cancer ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Cancer Cells ◽  
Breast Tumor ◽  
Breast Cancer Cells ◽  
Binding Assay ◽  
Metabolic Reprogramming ◽  
Cellular Lipid

Abstract Background Adiponectin, the most abundant adipokine derived from adipose tissue, exhibits a potent suppressive effect on the growth of breast cancer cells; however, the underlying molecular mechanisms for this effect are not completely understood. Fatty acid metabolic reprogramming has recently been recognized as a crucial driver of cancer progression. Adiponectin demonstrates a wide range of metabolic activities for the modulation of lipid metabolism under physiological conditions. However, the biological actions of adiponectin in cancer-specific lipid metabolism and its role in the regulation of cancer cell growth remain elusive. Methods The effects of adiponectin on fatty acid metabolism were evaluated by measuring the cellular neutral lipid pool, free fatty acid level, and fatty acid oxidation (FAO). Colocalization between fluorescent-labeled lipid droplets and LC3/lysosomes was employed to detect lipophagy activation. Cell viability and apoptosis were examined by MTS assay, caspase-3/7 activity measurement, TUNEL assay, and Annexin V binding assay. Gene expression was determined by real time-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis. The transcriptional activity of SREBP-1 was examined by a specific dsDNA binding assay. The modulatory roles of SIRT-1 and adiponectin-activated mediators were confirmed by gene silencing and/or using their pharmacological inhibitors. Observations from in vitro assays were further validated in an MDA-MB-231 orthotopic breast tumor model. Results Globular adiponectin (gAcrp) prominently decreased the cellular lipid pool in different breast cancer cells. The cellular lipid deficiency promoted apoptosis by causing disruption of lipid rafts and blocking raft-associated signal transduction. Mechanistically, dysregulated cellular lipid homeostasis by adiponectin was induced by two concerted actions: 1) suppression of fatty acid synthesis (FAS) through downregulation of SREBP-1 and FAS-related enzymes, and 2) stimulation of lipophagy-mediated lipolysis and FAO. Notably, SIRT-1 induction critically contributed to the adiponectin-induced metabolic alterations. Finally, fatty acid metabolic remodeling by adiponectin and the key role of SIRT-1 were confirmed in nude mice bearing breast tumor xenografts. Conclusion This study elucidates the multifaceted role of adiponectin in tumor fatty acid metabolic reprogramming and provides evidence for the connection between its metabolic actions and suppression of breast cancer.

scholarly journals Noninvasive imaging identifies new roles for cyclooxygenase-2 in choline and lipid metabolism of human breast cancer cells

2011 ◽  
Vol 25 (5) ◽  
pp. 746-754 ◽  
Author(s):  
Tariq Shah ◽  
Ioannis Stasinopoulos ◽  
Flonne Wildes ◽  
Samata Kakkad ◽  
Dmitri Artemov ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Lipid Metabolism ◽  
Cancer Cells ◽  
Human Breast Cancer ◽  
Breast Cancer Cells ◽  
Noninvasive Imaging ◽  
Cyclooxygenase 2 ◽  
Human Breast Cancer Cells ◽  
Human Breast
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