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Metabolites 2018, 8(4), 95; https://doi.org/10.3390/metabo8040095

Dynamic Metabolic Response to Adriamycin-Induced Senescence in Breast Cancer Cells

1
College of Life Sciences, South China Normal University, 55 Zhongshan Avenue West, Guangzhou 510631, China
2
Mitochondria and Metabolism Center, Department of Anesthesiology and Pain Medicine, University of Washington, 850 Republican Street, Seattle, WA 98109, USA
3
College of Plant Protection, Southwest University, 2 Tiansheng Road, Chongqing 400715, China
4
Chemistry and Biochemistry Department, California State Polytechnic University, Pomona, CA 91768, USA
5
Fred Hutchinson Cancer Research Center, 1100 Fairview Avenue N., Seattle, WA 98109, USA
*
Author to whom correspondence should be addressed.
Received: 31 October 2018 / Revised: 10 December 2018 / Accepted: 11 December 2018 / Published: 15 December 2018
(This article belongs to the Special Issue Cancer Metabolomics 2018)
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Abstract

Cellular senescence displays a heterogeneous set of phenotypes linked to tumor suppression; however, after drug treatment, senescence may also be involved in stable or recurrent cancer. Metabolic changes during senescence can provide detailed information on cellular status and may also have implications for the development of effective treatment strategies. The metabolic response to Adriamycin (ADR) treatment, which causes senescence as well as cell death, was obtained with the aid of metabolic profiling and isotope tracing in two human breast cancer cell lines, MCF7 and MDA-MB-231. After 5 days of ADR treatment, more than 60% of remaining, intact cells entered into a senescent state, characterized by enlarged and flattened morphology and positive blue staining using SA-β-gal. Metabolic trajectory analysis showed that the two cell lines’ responses were significantly different and were divided into two distinct stages. The metabolic shift from the first stage to the second was reflected by a partial recovery of the TCA cycle, as well as amino acid and lipid metabolisms. Isotope tracing analysis indicated that the higher level of glutamine metabolism helped maintain senescence. The results suggest that the dynamic changes during senescence indicate a multi-step process involving important metabolic pathways which might allow breast cancer cells to adapt to persistent ADR treatment, while the higher level of anapleurosis may be important for maintaining the senescent state. Ultimately, a better understanding of metabolic changes during senescence might provide targets for cancer therapy and tumor eradication. View Full-Text
Keywords: senescence MCF7; MDA-MB-231; metabolomics; isotope tracing analysis; gas chromatography–mass spectrometry (GC–MS) senescence MCF7; MDA-MB-231; metabolomics; isotope tracing analysis; gas chromatography–mass spectrometry (GC–MS)
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You, R.; Dai, J.; Zhang, P.; Barding, G.A., Jr.; Raftery, D. Dynamic Metabolic Response to Adriamycin-Induced Senescence in Breast Cancer Cells. Metabolites 2018, 8, 95.

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