By Cindy L.A. Jones, Ph.D.
Essential oils, the highly concentrated volatile, aromatic essences of
plants, are a mainstay of aromatherapy but are also used in flavoring, perfumes
and even as solvents. Researchers now think that two components of orange oil
and lavender oil are a good bet to prevent and treat cancer.
Most essential oils contain monoterpenes, compounds that contain 10 carbon
molecules often arranged in a ring. Monoterpenes are formed in the mevalonic
acid pathway in plants. This is the same pathway that makes cholesterol in
animals and humans. Early on, cancer researchers realized that some aspects of
cholesterol metabolism were involved in cancer growth. They then discovered
that plant monoterpenes interfered with animal cholesterol synthesis, thereby
reducing cholesterol levels and reducing tumor formation in animals.
Limonene and Perillyl Alcohol
Two widely studied monoterpenes are being evaluated for their anticancer
activity, limonene from orange peel (Citrus sinensis) and perillyl alcohol from
lavender (Lavandula angustifolia). Because limonene and perillyl affect the pathway that produces cholesterol,
they can inhibit cholesterol synthesis, thereby eliminating a minor contributor
to cancer formation. Monoterpenes also increase the levels of liver enzymes
involved in detoxifying carcinogens, an effect that decreases the possibility
carcinogens will cause cellular damage. In addition, monoterpenes stimulate
apoptosis, a cellular self-destruction mechanism triggered when a cell's DNA is
badly damaged. This safety feature is generally activated before a cell becomes
cancerous. Finally, monoterpenes inhibit protein isoprenylation. The cell uses
this process to help a protein, in this case the ras protein involved in cell
growth, find its proper location within the cell. If ras is not in the right
place, it becomes overactive and can spur cancerous cell growth.
Where Do They Come From? Most plant matter contains a wide variety of
monoterpenes. Rich sources include: herbs, spices, wine, essential oils, eggs,
olive & palm oil, rice bran oil, barley oil, and dairy products.
Laboratory animal studies demonstrate that these two monoterpenes inhibit
the formation of chemically induced breast, colon, liver, skin and pancreatic
tumors. For example, animals fed a diet containing 5 percent orange peel oil
had a significantly reduced risk of developing mammary tumors when treated with
the chemical tumor inducer DMBA. Similarly, animals fed a 5-percent limonene
diet had less chance of mammary tumor growth. Researchers noticed that in this
experiment rat tumors also regressed, suggesting limonene may treat existing
cancer as well as prevent it.
New drugs typically undergo three phases of clinical tests, each more
rigorous than the previous: Phase I trials establish a toxic human dose, phase
II trials determine a therapeutic dose and how it is metabolized, and phase III
trials determine drug effectiveness. Extensive animal studies are done before
phase I trials begin.
Phase I trials have so far shown that limonene is well tolerated by cancer
patients and has little toxicity. Phase II trials, to test how well limonene
actually works to reduce cancer, are under way at several institutions
including the National Cancer Institute (NCI) in Bethesda, Md. In other research, perillyl alcohol, a related compound, was found to be
five times as active as limonene in regressing tumors. A diet of 2.5 percent
perillyl alcohol caused 75 percent of chemically induced rat mammary tumors to
regress. Perillyl alcohol is now being tested in NCI-sponsored phase I clinical
trials as a treatment for advanced breast, ovarian and prostatic cancers at the
University of Wisconsin, Madison. Researchers speculate that perillyl alcohol
may also be effective against pancreatic cancer, which is extremely difficult
to treat.
The amount of monoterpenes needed to prevent cancer in humans is not
established. Toxicity studies are incomplete, but the high doses required for
chemotherapy may cause kidney damage and gastrointestinal problems. Both orange
and lavender essential oils are safe to ingest; in fact, orange oil is a common
food additive used for flavoring.
Few drugs have been developed that effectively treat cancer, so NCI is
constantly searching for potential drug candidates. Many of these candidates,
like limonene and perillyl alcohol, are natural products from herbs. For now
though, these two concentrated substances remain in the realm of the
laboratory, the doses being used in clinical trials are intended for treating
cancer and must be monitored by a physician.
References
1. Elson CE, Yu SG. The chemoprevention of cancer by mevalonate-derived
constituents of fruits and vegetables. J Nutr 1994;124:607-14.
2. Gould MN. Cancer chemoprevention and therapy by monoterpenes. Environ
Health Perspect 1997;105:S977-9.
3. Mills JJ, et al. Induction of apoptosis in liver tumors by the
monoterpene perillyl alcohol. Cancer Res 1995; 55:979-83.
4. Hohl RJ. Monoterpenes as regulators of malignant cell proliferation. In:
American Institute for Cancer Research. Dietary Phytochemicals in Cancer
Prevention and Treatment. New York: Plenum Press;1996.
5. Elson CE. Suppression of mevalonate pathway activities by dietary
isoprenoids: protective roles in cancer and cardiovascular disease. J Nutr
1995;125:1666S-72S.
6. [Anonymous]. Clinical Development Plan: l-Perillyl Alcohol, J Cellular
Biochem 1996;26S:137-48.
7. Crowell PL, et al. Antitumor effects of limonene and perillyl alcohol
against pancreatic and breast cancer. In: American Institute for Cancer
Research. Dietary Phytochemicals in Cancer Prevention and Treatment. New York:
Plenum Press;1996.
8. Vigushin DM, et al. Phase I and pharmacokinetic study of d-limonene in
patients with advanced cancer. Cancer Research Campaign Phase I/II Clinical
Trials Committee. Cancer Chemother & Pharmacol 1998;42:111-17.
9. Ziegler J. Raloxifen, retinoids and lavender: "me too"
tamoxifen alternatives under study. J Natl Canc Inst 1996;88:1100-1.
10. Stark MJ, et al. Chemotherapy of pancreatic cancer with the monoterpene
perillyl alcohol. Cancer Letters 1995; 96:15-21.
Originally printed April 1999 Nutrition Science News