Impact of chemotherapy on metabolic reprogramming: Characterization of the metabolic profile of breast cancer MDA-MB-231 cells using 1H HR-MAS NMR spectroscopy

Abstract

Doxorubicin, cisplatin, and tamoxifen are part of many chemotherapeutic regimens. However, studies investigating the effect of chemotherapy on the metabolism of breast cancer cells are still limited. We used 1H high-resolution magic angle spinning (HR-MAS) NMR spectroscopy to study the metabolic profile of human breast cancer MDA-MB-231 cells either untreated (control) or treated with tamoxifen, cisplatin, and doxorubicin. 1H HR-MAS NMR single pulse spectra evidenced signals from all mobile cell compounds, including fatty acids (membranes), water-soluble proteins, and metabolites. NMR spectra showed that phosphocholine (i.e., a biomarker of breast cancer malignant transformation) signals were stronger in control than in treated cells, but significantly decreased upon treatment with tamoxifen/cisplatin. NMR spectra acquired with Carr-Purcell-Meiboom-Gill (CPMG) pulse sequence were interpreted only qualitatively because signal areas were attenuated according to their transverse relaxation times (T2). The CPMG method was used to identify soluble metabolites such as organic acids, amino acids, choline and derivatives, taurine, guanidine acetate, tyrosine, and phenylalanine. The fatty acid variations observed by single pulse as well as the lactate, acetate, glycine, and phosphocholine variations observed through CPMG 1H HR-MAS NMR have potential to characterize both responder and non-responder tumors in a molecular level. Additionally, we emphasized that comparable tumors (i.e., with the same origin, in this case breast cancer) may respond totally differently to chemotherapy. Our observations reinforce the theory that alterations in cellular metabolism may contribute to the development of a malignant phenotype and cell resistance.