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LE Magazine March 2001
In The News
Lovastatin shows potent anti-cancer
effects
 In 1997, The Life Extension Foundation published
a protocol suggesting that cancer patients ask their
oncologist to consider prescribing the drug lovastatin (80 mg
a day) as an adjuvant therapy. This recommendation was based
on scientific studies indicating that lovastatin interfered
with the cancer cell growth cycle and might be synergistic
with conventional therapies in inducing apoptosis (programmed
cell death). Since 1997, a number of studies have
substantiated the potential benefit of lovastatin in treating
a wide range of cancers. In a new study published in the
journal Clinical Cancer Research (January 2001), lovastatin
demonstrated pronounced effects in inducing cancer cell
apoptosis in certain types of cancer. The scientists who
conducted this study showed that lovastatin worked
particularly well in the following cancer cells: acute myeloid
leukemia, neuroblastoma, squamous cell carcinoma of the
cervix, juvenile monomyelocytic leukemia, head and neck
squamous cell carcinoma, medullobastoma and rhabdomyosarcoma.
In discussing the results of their most recent research, the
scientists pointed to a previous five-year study on 745 people
taking lovastatin (to reduce their high cholesterol) that
showed that these subjects had a lower than expected incidence
of cancer. Most interesting was that in this group of 745
people taking lovastatin for 5-years, the incidences of
prostate and breast cancer was as expected, whereas there were
no cases of lovastatin-sensitive cancers observed. The
scientists suggested that these findings indicated that
lovastatin may prevent certain types of cancer from developing
in the first place. In this study published in Clinical Cancer
Research , the scientists noted that "lovastatin has the
potential as an immediate, novel therapeutic approach in the
treatment of these responsive tumors. Lovastatin induced a
specific apoptotic response in these tumor cells within
achievable therapeutic range and it (lovastatin) has a proven
record in the clinic as a safe and effective drug." The
scientists related a case history of a patient with acute
myeloid leukemia treated at their institution using lovastatin
at the high dose of 2 milligrams per kilogram of body weight
per day for 52 consecutive days. For a person weighing 154
pounds, this would mean a daily dose of lovastatin of 140 mg.
The patient taking this high-dose lovastatin demonstrated
control of leukemic blast counts that lasted more than six
months after cessation of treatment.
There are now Phase I clinical trials scheduled to evaluate
the toxicity and efficacy of low-dose lovastatin in the
treatment of recurrent acute myeloid leukemia, head and neck
squamous cell carcinomas, and cervical cancer. The Life
Extension Foundation does not recommend that members enter
these Phase I clinical trials, as they will restrict the use
of other synergistic cancer therapies and may use a dose of
lovastatin too low to provide optimal benefit. Instead,
members should ask there doctor to prescribe a higher dose
lovastatin and have a complete blood chemistry test performed
every two weeks for the first two months of therapy to make
sure lovastatin is not causing liver or muscle damage. Monthly
blood chemistry tests should be done as long as high dose
lovastatin is used.
Previous studies have indicated that lovastatin and other
fat-soluble "statin" drugs are also effective against
pancreatic, colon, liver and thyroid tumors. There are several
mechanisms of action that have been proposed for lovastatin's
anti-cancer actions, including suppressing the over-expression
of the RAS oncogene and interfering with the mevalonate
pathway used by some cancer cells in the G1 phase of the cell
cycle. Lovastatin (sold under the trade name Mevacor) is one
fat-soluble "statin" drug available by prescription. Other
fat-soluble statin drugs include Zocor and Lipitor. The
popular cholesterol-lowering drug called Pravachol is a
water-soluble "statin" that may not work as well against
cancer as the fat-soluble "statin" drugs. For further
information on the use of "statin" drugs to treat cancer refer
to the Cancer (Adjuvant) Treatment section of the book Disease
Prevention and Treatment or view this protocol on the
Foundation's website at www.lef.org
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Soy and DHEA
make women happy
Japanese researchers have reported that the benefits of
soy may include psychological well-being. Women who eat soy
products are less anxious, fearful and depressed, according
to a new study. All the women who participated were
healthy, and none were on hormone replacement therapy. The
beneficial effects of soy may be due to its estrogen-like
actions. Genistein, a component of soy, interacts with
estrogen and GABA receptors in the brain. Information was
obtained from 103 Japanese women, average age 54. The women
then completed the Center for Epidemiologic Studies
Depression (CES-D) Scale and the psychological part of the
General Health Questionnaire (GHQ). Women who ate the most
soy scored the best on these tests. Neither estradiol nor
sex hormone binding globulin correlated with mood, but
dehydroepiandrosterone did. DHEA, as it is known, was also
higher in the study participants who were happier. It's
unknown whether there is a correlation between soy and
DHEA, but previous studies have shown a positive effect of
DHEA on mood in older people.
 DHEA is
an androgen-type hormone that is converted to both estrogen
and testosterone. Testosterone increases libido in some
women. Estrogen replacement therapy (drug therapy) has
proven beneficial in enhancing mood in some older women.
According to a meta-analysis published in 1999, “At
this time, estrogen therapy [synthetic estrogen drugs] for
the treatment of depression in peri and postmenopausal
women may be useful, but confirmatory studies are still
lacking.” The possible benefits of drug therapy should
be weighed against the risks and side effects, which are
substantial.
Archer JS. 1999. NAMS/Solvay Resident
Essay Aware. Relationship between estrogen, serotonin, and
depression. Menopause
6:71-8.
Morales AJ, et al. 1994. Effects of replacement dose of
dehydroepiandrosterone in men and women of advancing age.
J Clin Endocrinol Metab
78:1360-67.
Nagata C, et al., 2000. Serum concentrations of estradiol
and dehydroepiandrosterone sulfate and soy product intake
in relation to psychologic well-being in peri and
postmenopausal Japanese women. Metabolism 49:1561-64.
Wolkowitz OM, et al. 1995. Antidepressant and
cognition-enhancing effects of DHEA in major depression.
Ann NY Acad Sci
774:b337-39.
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I3C and breast cancer
A new study confirms that invasive breast cancer is less
likely to occur when the body converts estrogen a certain way.
The study reports a 40% reduction in risk when the body
metabolizes estrogen into the less potent 2-hydroxyestrone
instead of 16a-hydroxyestrone. These metabolites have
important differences, one being that 16a-hydroxyestrone has
stronger estrogenic activity than 2-hydroxyestrone which is a
weak form of estrogen. The more 2-hydroxyestrone a woman has
in her body, the less likely she will have the strong
16a-hydroxyestrone that can drive cancer growth. The findings
are based on data from 144 Italian women with breast cancer
out of 10,000 who participated in a study on how hormones and
diet might cause the disease. 16a-hydroxyestrone is higher in
women with breast cancer, and correlates with a greater
incidence of mammary tumors in mice.
One of the things that changes the way estrogen is
metabolized is indole-3-carbinol (I3C), a substance in
cruciferous vegetables such as cabbage, cauliflower and
broccoli. I3C has been purified, and is sold as a supplement.
In studies where the supplement is used, I3C causes an
increase in the amount of 2-hydroxyestrone. That in turn, puts
a damper on cancer growth encouraged by 16a-hydroxyestrone.
I3C doesn't affect 16a-hydroxyestrone directly. Studies show
that I3C can also reduce DNA damage caused by heterocyclic
amines (cancer-causing molecules that arise when meat is
cooked), and cigarette smoke. It also inhibits the formation
of 4-hydroxyestrone which is carcinogenic. In cancer cells, it
induces apoptosis (cell death), and stops the cell cycle. In
mice, I3C prevents cervical cancer caused by papilloma virus.
It may also affect the growth of prostate cancer (although
studies have not been done). A male hormone,
16a-hydroxytestosterone, is transformed through the same
mechanism as 16a-hydroxyestrone in women.
Arif JM, et al. 2000. Inhibition of
cigarette smoke-related DNA adducts in rat tissues by
indole-3-carbinol. Mutat
Res 452:11-18.
He YH, et al. 2000. Indole-2-carbinol as a chemopreventive
agent in 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine
(PhIP) carcinogenesis: inhibition of PhIP-DNA adduct
formation, acceleration of PhIP metaqbolism, and induction of
cytochrome P450 in female F344 rats. Food Chem Toxicol 38:15-23.
Jin L, et al. 1999. Indole-3-carbinol prevents cervical
cancer in human papilloma virus type 16 (HPV16) transgenic
mice. Cancer Res
59:3991-97.
Muti P, et al. 2000. Estrogen metabolism and risk of breast
cancer: a prospective study of the 2:16 -hydroxyestrone ratio
in premenopausal and postmenopausal women. Epidemiology 11:635-40.
Schneider JD, et al. 1982. Abnormal oxidative metabolism of
estradiol in women with breast cancer. Proc Natl Acad Sci USA
79:3047-51.
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