Effects of garcinol and its derivatives on intestinal cell growth: Inhibitory effects and autoxidation-dependent growth-stimulatory effects

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 oxida...

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Published in:Free radical biology & medicine 2007-04, Vol.42 (8), p.1211-1221
Main Authors: Hong, Jungil, Kwon, Seok Joo, Sang, Shengmin, Ju, Jihyeung, Zhou, Jian-nian, Ho, Chi-Tang, Huang, Mou-Tuan, Yang, Chung S.
Format: Article
Language:English
Subjects:
Apoptosis - drug effects
Autoxidation
Cell Cycle - drug effects
Cell Division - drug effects
Cell growth
Cell Line
Cell Line, Tumor
Colon cancer
Colonic Neoplasms
Free radicals
Garcinol
Humans
Hydrogen peroxide
Intestinal cell
Intestines - cytology
Intestines - drug effects
Kinetics
Plant Extracts - pharmacology
Terpenes - pharmacology
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Summary: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 IC 50 of 3.2–21.4 μM after a 3-day treatment. Garcim-1 exhibited the strongest effect with IC 50 of 3.2–5.9 μM. 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 μM) 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 IC 50 to 1.5 from 11.8 μM in 72-h incubations and to 3 from 38 μM 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 (
ISSN:0891-5849
1873-4596
DOI:10.1016/j.freeradbiomed.2007.01.016