3 alpha-Hydroxymasticadienonic Acid As an Antiproliferative Agent That Impairs Mitochondrial Functions
Por:
Via, LD, Braga A., García-Argáez A.N., Martínez-Vázquez M., Toninello A.
Publicada:
1 abr 2012
Resumen:
Previous investigations on the biological effects of 3 alpha-hydroxymasticadienonic acid (1) have demonstrated both anti-inflammatory and cytotoxic activities. However, neither the molecular mechanism of cytotoxic action nor the possible intracellular target(s) have been reported so far for this compound. The crucial role played by mitochondria on both cell survival and death, due to production of ATP and intrinsic apoptosis, respectively, prompted a study of the effect of 1 on isolated rat liver mitochondria. It was found that 1 causes a dose dependent impairment of mitochondrial bioenergetic parameters, such as the respiratory control index and transmembrane electrical potential. Moreover, in the presence of Ca2+, at a 10 mu M concentration, 1 resulted in the induction of membrane permeability transition by oxidative stress, leading to the release of pro-apoptotic factors. At a 100 mu M concentration, compound 1 affected mitochondrial Ca2+ transport by inhibiting the accumulation of
Filiaciones:
Braga A.:
Department of Pharmaceutical Sciences, University of Padova, Via F. Marzolo, 5, 35131 Padova, Italy
García-Argáez A.N.:
Department of Pharmaceutical Sciences, University of Padova, Via F. Marzolo, 5, 35131 Padova, Italy
Martínez-Vázquez M.:
Univ Nacl Autonoma Mexico, Inst Quim, Mexico City 04510, DF, Mexico
Instituto de Química, Universidad Nacional Autónoma de México, Circuito Exterior, Ciudad Universitaria, Coyoacán 04510, México D. F., Mexico
Toninello A.:
Department of Biological Chemistry, University of Padova, Via G. Colombo, 3, 35121 Padova, Italy
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