A cytotoxic Petiveria alliacea dry extract induces ATP depletion and decreases β-F1-ATPase expression in breast cancer cells and promotes survival in tumor-bearing mice

Abstract Metabolic plasticity in cancer cells assures cell survival and cell proliferation under variable levels of oxygen and nutrients. Therefore, new anticancer treatments endeavor to target such plasticity by modifying main metabolic pathways as glycolysis or oxidative phosphorylation. In American traditional medicine Petiveria alliacea L., Phytolaccacea, leaf extracts have been used for leukemia and breast cancer treatments. Herein, we study cytotoxicity and antitumoral effects of P. alliacea extract in tumor/non-tumorigenic cell lines and murine breast cancer model. Breast cancer cells treated with P. alliacea dry extract showed reduction in β-F1-ATPase expression, glycolytic flux triggering diminished intracellular ATP levels, mitochondrial basal respiration and oxygen consumption. Consequently, a decline in cell proliferation was observed in conventional and three-dimension spheres breast cancer cells culture. Additionally, in vivo treatment of BALB/c mice transplanted with the murine breast cancer TS/A tumor showed that P. alliacea extract via i.p. decreases the primary tumor growth and increases survival in the TS/A model.

Miocarditis de células gigantes / Giant cell myocarditis

Resumen La miocarditis de células gigantes es una enfermedad rara, con gran impacto en cuanto a la mortalidad de pacientes usualmente jóvenes y sanos, que provoca diversas presentaciones clínicas como: la falla cardiaca, las arritmias ventriculares refractarias y los bloqueos. Su diagnóstico se establece con un alto índice de sospecha y con la confirmación por medio de la biopsia endomiocárdica por presencia de células gigantes multinucleadas sin presencia de un patrón granulomatoso. Su tratamiento inmunomodulador ha cambiado de manera importante en los últimos años, con una evidente disminución en los índices de mortalidad, aunque aún se requieren estrategias complementarias de manejo como el uso de dispositivos intracardiacos y/o el trasplante cardiaco para lograr mejores desenlaces a largo plazo.

Abstract Giant cell myocarditis is a rare condition with a great impact with regards to mortality of otherwise young and healthy patients, causing multiple clinical presentations, such as heart failure, refractory ventricular arrhythmias and blocks. Its diagnosis is reached with a high degree of suspicion and with the confirmation by means of a endomyocardial biopsy with the presence of multinucleated giant cells without a granulomatous pattern. Its immunomodulatory treatment has considerably changed during the last years, with a clear reduction in mortality rates, though complementary management strategies are still required, such as the use of intracardiac devices and/or heart transplantation in order to achieve better longterm results.