Apoptotic and necrotic effects of hexanedione derivatives on the human neuroblastoma line SK-N-SH

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

“…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]. Another possible explanation for the increased sensitivity of the SH-SY5Y line may be linked with the relatively high but consistent background apoptosis seen in the SH-SY5Y cells in this study compared to that of the SK-N-SH line in previous work [8]. A number of factors may influence the predisposition of different neuroblastoma lines to enter apoptosis, such as effects on protein kinase C, Bcl-2 and the long spliced variant of the G protein G1 s-L [14,15], as well as differential responses to growth factors [9].…”

“…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.…”

“…Using flow cytometry in a previous study with the SK-N-SH line, it was determined that 2,5-hexanedione caused apoptosis over 48 hr in the concentration range of 9-17 mM [8]. In this report, after allowing for the increased SH-SY5Y background apoptosis compared to the SK-N-SH cells, the SH-SY5Y line showed a similar pattern of DNA checkpoint in response to cellular damage compared to the SK-N-SH cell line.…”

“…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].…”

“…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].…”