Mitochondrial activity, function and differentiation
strongly impact the antitumoral ability of melatonin
which involves, among others, the activation of intrinsic
apoptotic pathways, in P19 embryonal carcinoma
cells as well as in other types of cancer cells [24]. It is
known that AIF controls programmed cells death during
early morphogenesis and that its genetic inactivation
renders embryonic stem cells resistant to cell death [67].
Consequently, the mechanism of caspase-3-independent
cell death, stimulation of mitochondrial differentiation and
metabolism, with consequent disruption of the Warburg
effect constitute promissory strategies when targeting
resistant cancer cells with an embryonic signature.