Metabolic transformation of breast cancer in a MCF-7 xenograft mouse model and inhibitory effect of volatile oil from Saussurea lappa Decne treatment

Breast cancer results from multi-step carcinogenesis, and the transforming process from normal to malignant cells is associated with profound metabolic disturbances. The metabolic transformation due to interplay between tumor and host during the development of breast cancer and its implications for breast cancer therapy have not been extensively investigated. Here, we report a metabonomic study on MCF-7 xenograft mice to delineate characteristic metabolic transformation during the development of breast cancer using a comprehensive two-dimensional gas chromatography-time-of-flight mass spectrometry (GCxGC-TOF/MS) and an ultra performance liquid chromatography-quadrupole time-of-flight mass spectrometry. Volatile oil extracted from Saussurea lappa Decne (VOSL), and Costunolide and Dehydrocostus lactone (Cos-Dehy), isolated from VOSL, were used to treat the MCF-7 xenograft mice to evaluate their efficiency and to investigate their pharmacological mechanism on inhibiting the growth of tumor. The dynamic changes of serum and urine metabolic profiles indicated that both VOSL and Cos-Dehy were able to attenuate metabolic perturbation MCF-7 xenograft mice, which is consistent with their efficiency that VOSL and Cos-Dehy significantly inhibit the growth of MCF-7 xenograft tumor. Significant alterations of key metabolic pathways, including elevated glycolysis and steroid hormone metabolism, and decreased unsaturated fatty acids metabolism, were observed in MCF-7 xenograft mice, which were attenuated or normalized by VOSL and Cos-Dehy treatment. Arachidonate, docosahexaenoic acid, eicosapentaenoic acid, linoleate, dihomo-gamma-linolenate, 20 alpha-hydroxyprogesterone, and cortisone were selected as a panel of candidate pathological biomarkers of MCF-7 xenografts, which may be further developed to be valuable diagnostic markers for the early detection of breast cancer.