Celecoxib and Dimethylcelecoxib Block Oxidative Phosphorylation, Epithelial-Mesenchymal Transition and Invasiveness in Breast Cancer Stem Cells.

Background: The major hurdles for successful cancer treatment are drug resistance and invasiveness developed by breast cancer stem cells (BCSC).

Objective: As these two processes are highly energy-dependent, the identification of the main ATP supplier required for stem cell viability may result advantageous in the design of new therapeutic strategies to deter malignant carcinomas.

Methods: The energy metabolism (glycolysis and oxidative phosphorylation, OxPhos) was systematically analyzed by assessing relevant protein contents, enzyme activities, and pathway fluxes in BCSC.

Heart myxoma develops oncogenic and metastatic phenotype.

Purpose: Heart myxomas have been frequently considered as benign lesions associated with Carney's complex. However, after surgical removal, myxomas re-emerge causing dysfunctional heart.

Methods: To identify whether cardiac myxomas may develop a metastatic phenotype as occurs in malignant cancers, a profile of several proteins involved in malignancy such as oncogenes (c-MYC, K-RAS and H-RAS), cancer-associated metabolic transcriptional factors (HIF-1α, p53 and PPAR-γ) and epithelial-mesenchymal transition proteins (fibronectin, vimentin, β-catenin, SNAIL and MMP-9) were evaluated in seven samples from a cohort of patients with atrial and ventricular myxomas.

HPI/AMF inhibition halts the development of the aggressive phenotype of breast cancer stem cells.

Cancer stem cells are responsible for tumor recurrence and metastasis. A new highly reproducible procedure for human breast cancer MCF-7 stem cells (BCSC) isolation and selection was developed by using a combination of hypoxia/hypoglycemia plus taxol and adriamycin for 24h. The BCSC enriched fraction (i) expressed (2-15 times) the typical stemness protein markers CD44+, ALDH1A3 and Oct 3/4; (ii) increased its clonogenicity index (20-times), invasiveness profile (>70%), migration capacity (100%) and ability to form mammospheres, compared to its non-metastatic MCF-7 counterpart.