Induction of Cytoprotective Mechanisms by the Chemopreventive Isothiocyanate Sulforaphane in Rat and Murine Hepatoma Cell Lines

Sulforaphane [1-isothiocyanato-4(methylsulfinyl) butane, SN] is a well known cruciferous chemopreventive phytochemical that induces the anticarcinogenic enzyme quinone reductase (QR, NQO1, EC 1.6.99.2) and other phase II detoxification enzymes [1]. The present study aimed to investigate the induction of QR activity and heat shock protein 70 (HSP70) expression in the rat hepatoma (FGC4) and murine hepatoma (hepa1c1c7) cells by SN.

(A)

(B)Figure (1): Responses of FGC4 cells to SN treatment; induction of QR (A) and HSP70 (B).

Following 24 hours exposure to non-toxic concentrations of SN (as assessed by neutral red uptake), FGC4 cells were less sensitive to QR activity induction (Figure 1A) as compared to hepa1c1c7 (significant induction of 150%±16 vs. 440%±44, respectively at 6.25µM SN, p<0.01) which may be due to the high basal QR activity of FGC4 cells. In a preliminary experiment, SN had no effect on HSP70 expression in hepa1c1c7 (data not shown). Interestingly, SN significantly induced HSP70 expression in FGC4 (Figure 1B) as revealed by western blotting and densitometric analysis (250%±49 at 25µM SN, p<0.01). These data represent the first report of the induction of HSP70 expression in vitro by SN as a cytoprotective mechanism induced by this promising chemopreventive compound. In support of these data, Hu et al. [2] have very recently reported the induction of HSP70 genes in livers of SN- treated mice.

Acknowledgements: Egyptian Government, School of Biomedical Sciences (Nottingham, UK).

References: 1. Zhang, Y. et al. (1994), PNAS 91: 3147–3150. 2. Hu, R. et al. (2006), Cancer Lett. In press.