The toxicity of hexanedione isomers in neural and astrocytic cell lines

A Comparison of the Apoptotic and Cytotoxic Effects of Hexanedione Derivatives on Human Non‐Neuronal Lines and the Neuroblastoma Line SH‐SY5Y

“…Interestingly, in both α-diketones, there was a marked increase in their toxicity with the SH-SY5Y cells over 24 hr compared to 4 hr exposure. In comparison with a previous study, under identical conditions with the SK-N-SH line, the SH-SY5Y line in this report showed a 4-fold increase in sensitivity to α-diketone toxicity [7]. This sensitivity of the SH-SY5Y cells may be a consequence of their greater neuroblastic homogeneity compared to the SK-N-SH cells, which are a mixture of melanocytic/glial and neuroblastic cells [9].…”

“…However, it was apparent in this report even at the high initial 2,5-isomer concentrations evaluated, the SH-SY5Y cells were much more sensitive at 4 hr to the 2,5-derivative that the non-neural lines. This was underlined at 24 hr with the SH-SY5Y cells, although the HepG 2 and CaCo-2 cells also showed a marked increase in sensitivity to this agent over this time period; indeed, this increase appeared to conform with Haber's rule, where the IC 50 (mM) X duration of exposure (hr) = constant [3,7]. The 2,5-isomer is thought to be neurotoxic in man through its cross-linking of neurofilaments [1] that leads to axonal atrophy [3].…”

“…Previous studies have underlined the relative insensitivity of various neural cell lines to 2,5-hexanedione-mediated toxicity [7,8] over short-time periods of exposure. However, it was apparent in this report even at the high initial 2,5-isomer concentrations evaluated, the SH-SY5Y cells were much more sensitive at 4 hr to the 2,5-derivative that the non-neural lines.…”

“…In contrast, the 2,3-and 3,4-isomers have been generally viewed as non-toxic [2,5] although the 2,3-derivative induced mitotic chromosomal loss in the presence of an inducer of chromosomal malsegregation [6]. More recent studies have revealed the 2,3-and 3,4-isomers to be several fold more acutely toxic over 4 and 24 hr compared to the 2,5-isomer in a number of neural and astrocytic cell lines [7] and they are also capable of disrupting the cell cycle and causing apoptosis in the human SK-N-SH neuroblastoma cell line [8].…”

“…In contrast, the 2,3-and 3,4-isomers have been generally viewed as non-toxic [2,5] although the 2,3-derivative induced mitotic chromosomal loss in the presence of an inducer of chromosomal malsegregation [6]. More recent studies have revealed the 2,3-and 3,4-isomers to be several fold more acutely toxic over 4 and 24 hr compared to the 2,5-isomer in a number of neural and astrocytic cell lines [7] and they are also capable of disrupting the cell cycle and causing apoptosis in the human SK-N-SH neuroblastoma cell line [8].To date, there have been no comparative studies aimed at determining if the 2,3-and 3,4-hexanediones illustrate any degree of specific toxicity towards neuroblastoma lines or are cytotoxic to human cell lines in general. Hence, the cytotoxicity of the three hexanedione derivatives was evaluated using the MTT reduction assay in the SH-SY5Y line, a pure neuroblastic subclone of the SK-N-SH line, which is made up predominantly of neuroblastic and melanocytic/ glial cells and displays fewer neuronal characteristics than the SH-SY5Y's [9].…”