PLACENTAL GLUTATHIONE-S-TRANSFERASE (GST-P) INDUCTION AS A POTENTIAL MECHANISM FOR THE ANTICARCINOGENIC EFFECT OF THE COFFEE-SPECIFIC COMPONENTS CAFESTOL AND KAHWEOL
B. Schilter et al., PLACENTAL GLUTATHIONE-S-TRANSFERASE (GST-P) INDUCTION AS A POTENTIAL MECHANISM FOR THE ANTICARCINOGENIC EFFECT OF THE COFFEE-SPECIFIC COMPONENTS CAFESTOL AND KAHWEOL, Carcinogenesis, 17(11), 1996, pp. 2377-2384
The coffee specific diterpenes cafestol and kahweol (C+K) have been re
ported to be anti-carcinogenic in several animal models, It has been p
ostulated that this activity may be related to their ability to induce
glutathione S-transferases (GSTs). We investigated the influence of a
mixture of C+K, incorporated at various levels in the diet of Sprague
-Dawley rats, on the expression of different hepatic GST iso-enzymes.
Liver samples were examined using isoform-specific GST substrates and
antibodies, and highly selective oligomers were employed to determine
effects at the RNA level. A dose-dependent increase in general GST act
ivity was observed in male and female animals following 28 or 90 days
of treatment. A time-course study demonstrated that the maximal effect
was observed within 5 days of treatment, Little or no effect was foun
d on the activity of GST alpha and mu iso-enzymes, The most striking o
bservation was a dose-dependent induction of placental glutathione S-t
ransferase (GST-P) which could be demonstrated at the mRNA, protein an
d enzymatic levels, This effect was observed in both male and female r
ats, The maximal induction was attained within 5 days of treatment wit
h C+K, remained elevated with continued treatment, but was reversible
on withdrawal of treatment. Immunohistochemical examination of liver s
lices revealed a strong even distribution of GST-P expression througho
ut the acinus at the highest dose of C+K, while at lower doses the ind
uction of GST-P occurred predominantly in periportal hepatocytes. Ther
e was no indication of the presence of preneoplastic foci and, further
more, the effect of C+K on the GST-P was completely reversible, These
findings indicate that the anticarcinogenic mechanism of C+K may invol
ve a specific induction of GST-P and suggest a potential role for GST-
P in detoxifying carcinogenic compounds.