Novel metabolic aspects related to adenosine deaminase inhibition in a human astrocytoma cell line

Mitochondrial Damage and Apoptosis Induced by Adenosine Deaminase Inhibition and Deoxyadenosine in Human Neuroblastoma Cell Lines

“…The combination also induces cell death in the LAN5 neuroblastoma cell line. These findings, together with our previous observation of an apoptotic effect of the same treatment on a human tumoral cell line of astrocytic origin [Garcia‐Gil et al, , ] suggest long‐term implications for therapy of cancer affecting nervous system.…”

“…In previous papers we have demonstrated that treatment with dCF plus dAdo in a human astrocytoma cell line (ADF) induces apoptosis, interferes with glucose metabolism, since a reduction in lactate released in the medium is observed in treated cells as an event preceding caspase‐3 activation and cellular death, and reduces mROS in short‐time incubations, while an increase is observed in long‐time incubations. Antioxidants such as melatonin, Mito‐Q or N‐acetylcysteine did not increase survival while baicalein and nordihydroguaiaretic acid exerted a protective effect [Garcia‐Gil et al, , ]. In this paper we have demostrated that two human neuroblastoma cell lines (SH‐SY5Y and LAN5) are both sensitive to the cytotoxic action of dAdo and dCF in combination and we have further investigated the mechanism of apoptosis induced by dCF plus dAdo in the SH‐SY5Y cell line, a well suited cellular model for the understanding of the molecular pathways leading to apoptosis in neuroblastoma cells.…”

“…The decreased mitochondrial activity would result in oxidative phosphorylation impairment, however neuroblastoma cells do not appear to compensate it by increasing glycolysis because the formation of lactate is not affected by the combination. In contrast with neuroblastoma cells, in a previous paper we demonstrated that the presence of dAdo plus dCF appears to impair the uptake of glucose in astrocytoma cells, therefore decreasing significantly the concentration of lactate in the medium starting from 4 h of incubation [Garcia‐Gil et al, ]. This might reflect a different glucose metabolic profile of neuronal and astrocytic cells: indeed, it has been reported that to fulfill the greater energy needs of neurons, glial cells release lactate that is eventually taken up and oxidized in neurons [Pellerin and Magistretti, ].…”

“…It is conceivable that the neurological manifestations raise from an adverse effect exerted by Ado, dAdo and their derivatives on the development, differentiation, and functioning of nervous system [Takeda et al, ]. Taking the cue from these observations, in previous papers [Garcia‐Gil et al, , ] we have demonstrated that the combination of dCF and dAdo is toxic for a human astrocytoma cell line (ADF), a cellular model deriving from a type of tumor reported to be particularly resistant to chemotherapeutic approaches and often characterized by a poor prognosis [Ohgaki and Kleihues, ]. In order to obtain an overall view of the effect of dCF and dAdo on cells of the nervous system, we have extended our observations to human neuroblastoma cell lines, with the aim to assess whether cells of neuronal origin, besides those of glial origin, are sensitive to the treatment.…”

Purinergic signalling and cancer

“…Extracellular adenosine, acting via A 1 receptors, activates caspase-9 and then caspase-3 via two independent pathways, leading to cell death of RCR-1 rat astrocytoma cells predominately by apoptosis [648]. ADA inhibition induces apoptosis in a human astrocytoma cell line [649].…”