Geraniol, a Component of Plant Essential Oils, Inhibits Growth and Polyamine Biosynthesis in Human Colon Cancer Cells
+ Author Affiliations
- Dr. Francis Raul, IRCAD, 1, place de l'hôpital, BP 426, 67091 Strasbourg cedex, France. E-mail: francis.raul@ircad.ustrasbg.fr
Abstract
Geraniol and other monoterpenes found in essential oils of fruits and herbs have been suggested to represent a new class of agents for cancer chemoprevention. As a first step in clarifying the mode of action of geraniol on colon carcinogenesis, we studied its effects on the growth of a human colon cancer cell line (Caco-2). Geraniol (400 μM) caused a 70% inhibition of cell growth, with cells accumulating in the S transition phase of the cell cycle, and concomitant inhibition of DNA synthesis. No signs of cytotoxicity or apoptosis were detected. Geraniol caused a 50% decrease of ornithine decarboxylase activity, a key enzyme of polyamine biosynthesis, which is enhanced in cancer growth. This led to a 40% reduction of the intracellular pool of putrescine. Geraniol also activated the intracellular catabolism of polyamines, indicated by enhanced polyamine acetylation. These observations indicate that polyamine metabolism is presumably a target in the antiproliferative properties of geraniol.
Numerous epidemiological studies revealed that high consumption of fruits, vegetables, and other plant products may reduce the incidence and development of colorectal cancer (Tuyns et al., 1988; Steinmetz and Potter, 1991; Steinmetz et al., 1994). Since colorectal cancers are difficult to treat with existing therapeutic modalities, identifying dietary phytochemicals that have antitumor activity and investigating their mechanisms of action may lead to significant advances in the prevention of human cancer (Block et al., 1992). The monoterpenes, found in essential oils of citrus fruits, cherry, mint, and herbs, are non-nutritive dietary microconstituents mainly responsible for the distinctive fragrance of many plants. They are used as flavor additives in food, beverages, and perfumes.
Recents studies have shown that monoterpenes exert antitumor activities and suggest that these components are a new class of cancer chemopreventive agents (Elson and Yu, 1994; Kelloff et al., 1996; Crowell, 1999). Limonene, a main constituent of orange and citrus peel oils, has been reported to exert antitumor activity against mammary gland, lung, liver, stomach, and skin cancers in rodents (Elegbede et al., 1986; Wattenberg and Coccia, 1991; Crowell and Gould, 1994; Mills et al., 1995; Kawamori et al., 1996). Similarly, perillyl alcohol, a hydroxylated limonene analog, exhibits chemopreventive activity against liver, mammary gland, pancreas, and colon cancers in rodents (Haag and Gould, 1994; Stark et al., 1995; Reddy et al., 1997). More recently, geraniol, an acyclic monoterpene alcohol found in lemongrass and aromatic herb oils, has been shown to exert in vitro and in vivo antitumor activity against murine leukemia, hepatoma, and melanoma cells (Shoff et al., 1991; Yu et al., 1995; Burke et al., 1997).
No information is available on the potential effects of geraniol on colon cancer. Therefore, we examined its effect on Caco-2 cell growth, a human colonic cancer cell line. We also measured the effect of geraniol on polyamine metabolism, which is known to be enhanced in cancer cells and which might be one of the targets of the chemopreventive action of geraniol (Seiler et al., 1998).
...In conclusion, our results are the first to describe a potent antiproliferative effect of geraniol on the growth of human colon cancer cells. Geraniol has no cytotoxic effect, is mainly cytostatic, and inhibits DNA synthesis, leading to the accumulation of Caco-2 cells in the S phase. Inhibition of ODC expression may be one of several targets involved in the antiproliferative effects of geraniol. However, it remains to be determined whether polyamine depletion by itself is directly responsible for the observed antiproliferative effect. The low toxicity of geraniol makes it attractive for in vivo studies in colon cancer prevention and treatment.
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