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Comparative metabolomics of MCF-7 and MCF-7/TAMR identifies potential metabolic pathways in tamoxifen resistant breast cancer cells.
Mishra, Alok; Srivastava, Anubhav; Srivastava, Anshuman; Sharma, Lokendra Kumar; Mishra, Anand Kumar; Shrivastava, Ashutosh.
Afiliação
  • Mishra A; Center for Advance Research, Faculty of Medicine, King George's Medical University Lucknow, Uttar Pradesh 226003, India.
  • Srivastava A; Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences Lucknow, Uttar Pradesh 226014, India.
  • Srivastava A; Center for Advance Research, Faculty of Medicine, King George's Medical University Lucknow, Uttar Pradesh 226003, India.
  • Sharma LK; Department of Molecular Medicine and Biotechnology, Sanjay Gandhi Postgraduate Institute of Medical Sciences Lucknow, Uttar Pradesh 226014, India.
  • Mishra AK; Department of Endocrine Surgery, Faculty of Medicine, King George's Medical University Lucknow, Uttar Pradesh 226003, India.
  • Shrivastava A; Center for Advance Research, Faculty of Medicine, King George's Medical University Lucknow, Uttar Pradesh 226003, India.
Am J Transl Res ; 16(4): 1337-1352, 2024.
Article em En | MEDLINE | ID: mdl-38715825
ABSTRACT

OBJECTIVES:

Breast cancer is the most common cancer and the leading cause of cancer-related death among women. An Estrogen Receptor (ER) antagonist called tamoxifen is used as an adjuvant therapy for ER-positive breast cancers. Approximately 40% of patients develop tamoxifen resistance (TAMR) while receiving treatment. Cancer cells can rewire their metabolism to develop resistant phenotypes, and their metabolic state determines how receptive they are to chemotherapy.

METHODS:

Metabolite extraction from human MCF-7 and MCF-7/TAMR cells was done using the methanol-methanol-water extraction method. After treating the dried samples with methoxamine hydrochloride in pyridine, the samples were derivatized with 2,2,2-Trifluoro-N-methyl-N-(trimethylsilyl)-acetamide, and Chlorotrimethylsilane (MSTFA + 1% TMCS). The Gas chromatography/mass spectrometry (GC-MS) raw data were processed using MSdial and Metaboanalyst for analysis.

RESULTS:

Univariate analysis revealed that 35 metabolites were elevated in TAMR cells whereas 25 metabolites were downregulated. N-acetyl-D-glucosamine, lysine, uracil, tyrosine, alanine, and o-phosphoserine were upregulated in TAMR cells, while hydroxyproline, glutamine, N-acetyl-L-aspartic acid, threonic acid, pyroglutamic acid, glutamine, o-phosphoethanolamine, oxoglutaric acid, and myoinositol were found to be downregulated. Multivariate analysis revealed a distinct separation between the two cell lines, as evidenced by their metabolite levels. The enriched pathways of deregulated metabolites included valine, leucine, and isoleucine degradation, Citric Acid Cycle, Warburg effect, Malate-Aspartate shuttle, glucose-alanine cycle, propanoate metabolism, and Phospholipid biosynthesis.

CONCLUSION:

This study revealed dysregulation of various metabolic processes in TAMR cells, which may be crucial in elucidating the molecular basis of the mechanisms underlying acquired tamoxifen resistance.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Idioma: En Ano de publicação: 2024 Tipo de documento: Article