A comparison of the apoptotic and cytotoxic effects of hexanedione derivatives on human non-neuronal lines and the neuroblastoma line SH-SY5Y

Coleman, Michael D.; Zilz, Thomas R.; Griffiths, Helen R. and Woehrling, Elizabeth K. (2008). A comparison of the apoptotic and cytotoxic effects of hexanedione derivatives on human non-neuronal lines and the neuroblastoma line SH-SY5Y. Basic and Clinical Pharmacology and Toxicology, 102 (1), pp. 25-29.

Abstract

The effects of the alpha-diketone derivatives 2,3- and 3,4-hexanediones were investigated in three non-neuronal cell lines (MCF7, HepG2 and CaCo-2) as well as in the neuroblastoma line, SH-SY5Y. The MTT reduction assay was employed to determine the necrotic effects of the alpha-diketones and the neurotoxin 2,5-hexanedione over 4, 24 and 48 hr exposures. Flow cytometry was also used to study the effects of the three isomers on the cell cycle of the SH-SY5Y line only. With 2,5-hexanedione, the mean MTT IC50 decreased more than 10-fold from 4 to 48 hr. The toxicities of both alpha-diketones were similar, with a more than 18-fold increase in sensitivity of the SH-SY5Y at 24 hr compared to that of 4 hr. With flow cytometry at 48 hr, SH-SY5Y apoptosis with 2,5-hexanedione rose throughout the concentration range evaluated (0-30 mM) while 2,3- and 3,4-hexanediones showed apoptosis over the concentration range 1-1.6 mM, with 3,4-hexanedione being the more potent compared to the 2,3-isomer. At 1.6 mM nearly all the cells had entered apoptosis in the presence of the 3,4-isomer, (94.9 ± 1.4%) but only 57.5 ±4.1% of the 2,3-isomer-treated cells had reached that stage. The 2,3-and 3,4-isomers in diets alone may not pose a serious threat to human health. Further studies may be necessary to evaluate the effects of other dietary components on their toxicity. These alpha-diketones also display a degree of toxic selectivity towards neuroblastoma cells, which may have therapeutic implications.

Publication DOI: https://doi.org/10.1111/j.1742-7843.2007.00148.x
Divisions: Life & Health Sciences > Pharmacy
Life & Health Sciences > Biosciences
Life & Health Sciences
Uncontrolled Keywords: adenocarcinoma,apoptosis,breast neoplasms,hepatocellular carcinoma,tumor cell line,cell survival,colonic neoplasms,drug dose-response relationship,antitumor drug screening assays,tetrazolium salts,flow cytometry,formazans,hexanones,neuroblastoma,isomerism,neurons,Pharmacology,Toxicology
Published Date: 2008-01

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