Description
Triterpenoids are a large class of naturally occurring compounds, and some potentially interesting as
anticancer agents have been found to target mitochondria. The objective of the present work was to
investigate the mechanisms of mitochondrial toxicity induced by novel dimethylaminopyridine (DMAP)
derivatives of pentacyclic triterpenes, which were previously shown to inhibit the growth of melanoma
cells in vitro. MCF-7, Hs 578T and BJ cell lines, as well as isolated hepatic mitochondria, were used to
investigate direct mitochondrial effects. On isolated mitochondrial hepatic fractions, respiratory parameters,
mitochondrial transmembrane electric potential, induction of the mitochondrial permeability transition
(MPT) pore and ion transport-dependent osmotic swelling were measured. Our results indicate
that the DMAP triterpenoid derivatives lead to fragmentation and depolarization of the mitochondrial
network in situ, and to inhibition of uncoupled respiration, induction of the permeability transition pore
and depolarization of isolated hepatic mitochondria. The results show that mitochondrial toxicity is an
important component of the biological interaction of DMAP derivatives, which can explain the effects
observed in cancer cells. This work was supported by projects Pest-C/SAU/LA0001/2013–
2014 and PTDC/QUI-QUI/101409/2008 funded by Fundação para a
Ciência e a Tecnologia (FCT), Portugal, and cofinanced by: ‘COMPETE-
Programa Operacional Factores de Competitividade’, QREN
and European Union (FEDER-Fundo Europeu de Desenvolvimento Regional).
T.C.-O. was supported by the FCT postdoctoral fellowship
SFRH/BPD/34711/2007, T.L.S. supported by the FCT postdoctoral
fellowship SFRH/BPD/75959/2011, both co-financed by POPHPrograma
Operacional Potencial Humano, QREN and European
Union.
; Cunha-Oliveira, Teresa 
