Garcinol, a polyisoprenylated
benzophenone, from the Garcinia indica fruit rind, has been suggested to be an anti-inflammatory and anti-
cancer agent. To explore the possible use of this redox-sensitive compound as a
colon cancer preventive agent, we investigated the effects of
garcinol and its oxidative derivatives,
cambogin, garcim-1, and garcim-2, on the growth of HT-29 and HCT-116
colon cancer cells, as well as IEC-6 and INT-407 normal immortalized intestinal cells.
Garcinol and its derivatives showed potent growth-inhibitory effects on all intestinal cells, showing IC50 of 3.2-21.4 microM after a 3-day treatment. Garcim-1 exhibited the strongest effect with IC50 of 3.2-5.9 microM.
Garcinol was more effective in inhibiting growth of
cancer cells than that of normal immortalized cells. Flow-cytometric analysis showed increased sub-G1 cells by treatment with
garcinol and
cambogin. Induction of apoptosis by
garcinol and
cambogin (2-10 microM) was also observed based on
caspase-3 activation and enhanced
annexin V staining. The inhibitory effect of
garcinol on cell growth was much more pronounced in the absence of
fetal bovine serum (FBS), decreasing IC50 to 1.5 from 11.8 microM in 72-h incubations and to 3 from 38 microM in 24-h incubations, possibly due to the binding of
garcinol to FBS, which markedly reduced cellular levels of
garcinol. Under these conditions, redox reactions seem not to be involved in the inhibition. In contrast to the inhibitory effect, low concentrations (<1 microM) of
garcinol and
cambogin stimulated the growth of both normal and
cancer cells by 10-100%, and the activity seemed to be mediated by
reactive oxygen species. In the presence of
superoxide dismutase/
catalase or N-acetyl
cysteine, low concentrations of
garcinol (<1 microM) decreased cell growth.
Garcinol (0.5-1 microM) also increased the phosphorylation of extracellular signal-related
kinase 1/2 and AKT and the level of
survivin, and the effects were abolished in the presence of
superoxide dismutase/
catalase. Our results indicate that
garcinol and its derivatives can inhibit intestinal cell growth, but low concentrations of
garcinol can stimulate cell growth. It remains to be determined whether the currently observed stimulatory and inhibitory effects of
garcinol on colon cell growth occur in vivo.