Abstract |
The glyoxalase I inhibitor diester, S-p-bromobenzyl-glutathione cyclopentyl diester ( BrBzGSHCp2), inhibited the growth of human leukaemia 60 (HL60) cells in vitro. The median growth inhibitory concentration GC50 value of BrBzGSHCp2 was 4.23 +/- 0.001 microM (n = 21), and the median toxic concentration TC50 value was 8.86 +/- 0.01 microM (n = 21). BrBzGSHCp2 inhibited DNA synthesis in the third hr of incubation: the median inhibitory concentration IC50 value was 6.11 +/- 0.02 microM (n = 8). Incubation of HL60 cells with 10 microM BrBzGSHCp2 delivered the diester into cells: de-esterification of the diester there in lead to formation of the S-p-bromobenzylglutathione, inhibition of glyoxalase I activity in situ, increase in the methylglyoxal concentration after 1 hr, and induction of apoptosis after 6 hr. BrBzGSHCp2 (50-200 mg/kg) also inhibited the growth of murine adenocarcinoma 15A in vivo. Glyoxalase I inhibitor diesters may, therefore, inhibit tumour growth by inducing the accumulation of methylglyoxal in tumour cells, and induction of apoptosis.
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Authors | P J Thornalley, L G Edwards, Y Kang, C Wyatt, N Davies, M J Ladan, J Double |
Journal | Biochemical pharmacology
(Biochem Pharmacol)
Vol. 51
Issue 10
Pg. 1365-72
(May 17 1996)
ISSN: 0006-2952 [Print] England |
PMID | 8787553
(Publication Type: Journal Article)
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Chemical References |
- Esters
- S-4-bromobenzylglutathione cyclopentyl diester
- Glutathione
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Topics |
- Adenocarcinoma
(drug therapy)
- Animals
- Apoptosis
- Cell Count
(drug effects)
- Dose-Response Relationship, Drug
- Esters
(pharmacology)
- Glutathione
(analogs & derivatives, pharmacology)
- Humans
- In Vitro Techniques
- Leukemia
(drug therapy)
- Mice
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