1. Chem Pharm Bull (Tokyo). 2009 Jun;57(6):615-9.

Part 2: influence of 2-euryfuryl-1,4-naphthoquinone and its peri-hydroxy
derivatives on both cell death and metabolism of TLT cells, a murine hepatoma
cell line. modulation of cytotoxicity by vitamin C.

Benites J, Valderrama JA, Taper H, Buc Calderon P.

Departamento de Ciencias Químicas y Farmacéuticas, Universidad Arturo Prat,
Iquique, Chile, Avenida Arturo Prat 2120, Casilla 121, Iquique, Chile.

2-Euryfuryl-1,4-naphthoquinone C(1) and its 5- and 5,8-hydroxy derivatives C(2)
and C(3), were tested for their cytotoxicity towards transplantable liver tumor
(TLT) cells (a murine hepatoma cell line) in the absence and in the presence of
vitamin C. Cell death, caspase-3 activity and two metabolic end-points, namely
the intracellular content of ATP and glutathione (GSH), were employed to evaluate
their cytotoxicity. In a range of concentration from 0 to 10 microg/ml C(1) and
C(3) were non toxic against TLT cells, while compound C(2) killed about 50% of
cells by necrosis. Interestingly, the presence of vitamin C did not enhance the
cytolysis of C(2), but its addition exacerbated the effects of the three
compounds on both ATP and GSH contents, the two metabolic end points selected in 
our study. Our assumption is that the electron donor effect of the peri-hydroxyl 
substituents on euryfurylnaphthoquinones and the hydrogen bond between the
peri-hydroxy and quinone carbonyl groups influence the electron-acceptor
capability of the quinone nucleus and thus modifies the electron transfer from
ascorbate to the electroactive quinone nucleus. The combination of
euryfurylnaphthoquinones with vitamin C may be of potential clinical interest,
because cancer cells accumulate vitamin C, they are sensitive to an oxidant
insult and they depend on glycolysis (ATP formation) for their survival.

PMID: 19483346 [PubMed - indexed for MEDLINE]