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Life Extension Magazine

LE Magazine September 2001

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Studies from throughout the world that can help you live longer

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September 2001 Table of Contents

  1. Melatonin for treatment of dementia in the elderly
  2. Indole-3-carbinol inhibits human breast cancer
  3. Liver cancer after long-term tamoxifen therapy
  4. Anti-atherogenic effect of CoQ10
  5. Curcumin prevents radiation-induced breast cancer
  6. Curcumin modulates tumor remission
  7. Vitamin D3 vs. colon cancer?
  8. Curcumin and vitamin C inhibit free radicals
  9. Vitamin C and stomach cancer
  10. Silibinin inhibits proliferation of prostate cancer cells
  11. Curcumin may inhibit inflammation/blood clots

1. Melatonin for treatment of dementia in the elderly

Melatonin is a hormone produced and secreted by the pineal gland in response to darkness, which plays a major role in the induction and regulation of sleep. Melatonin production decreases with age. A study investigated the impact of melatonin administration as a clinical intervention for improving sleep and alleviating sundowning in 11 elderly nursing home residents who suffer from dementia. Age-related sleep disorders are frequently associated with disruption of circadian cycle rhythms, and sometimes with 'sundowning'. (Sundowning refers to the manifestation of agitation and/or confusion in the evening hours). Agitation has been linked to sleep disorders. Analysis after treatment with melatonin revealed a significant decrease in agitated behaviors in all three shifts, and a significant decrease in daytime sleepiness. There was also a small decrease in latency (time to fall asleep) during the evening shift. No significant changes were reported in night-time sleep ratings. Finding ways of decreasing sundowning in elderly persons may improve their well being, alleviate the burden of the caregivers, and even enable caregiving in a less restrictive environment.

ARCHIVES OF GERONTOLOGY AND GERIATRICS, 2000, Vol 31, Iss 1, pp 65-76


2. Indole-3-carbinol inhibits human breast cancer

Indole-3-carbinol (I3C) is a promising potent phytochemical in chemoprevention of breast cancer. Metastatic breast cancer is a devastating problem. A recent study is the first description of I3C that significantly inhibits the cell adhesion, spreading and invasion associated with an activation of PTEN (a tumor suppressor gene) and E-cadherin (a regulator of cell-to-cell adhesion) activity in human breast cancer cells. Therefore, I3C exhibits anti-cancer activities by suppressing breast tumor cell growth and metastatic spread. Therefore, the use of I3C may be helpful in limiting breast cancer invasion and metastasis.

BREAST CANCER RESEARCH AND TREATMENT, 2000, Vol 63, Iss 2, pp 147-152


3. Liver cancer after long-term tamoxifen therapy

This is a report of liver cancer after long term tamoxifen therapy in a 71-year-old woman. She was prescribed tamoxifen for 12 years following right mastectomy and axillary node clearance for breast cancer in 1985. In 1997, after she complained of abdominal pain and fullness, an abdominal ultrasound scan showed lesions in the right lobe of the liver. A biopsy showed primary hepatocellular carcinoma (HCC, the most common primary malignant liver tumor). Studies in rats suggest that tamoxifen is involved in the development of liver cancer, but studies in humans have failed to show any increased risk. However, these studies followed individuals for less than five years. An increased risk of HCC may not become apparent until after a decade or more of tamoxifen therapy. In addition, HCC in those treated with tamoxifen may be under-reported since there may be reluctance to biopsy liver tumors, which are assumed to be secondary breast cancer.

ANNALS OF ONCOLOGY, 2000, Vol 11, Iss 9, pp 1195-1196


4. Anti-atherogenic effect of CoQ10

Oxidation of low-density lipoprotein (LDL) lipid is implicated in atherogenesis and certain antioxidants inhibit atherosclerosis. CoQ10 inhibits LDL lipid peroxidation in vitro although it is not known whether such activity occurs in vivo, and, if so, whether this is anti-atherogenic. A study tested the effect of CoQ10 supplemention on lipoprotein lipid peroxidation of the aorta, and atherosclerosis in mice fed a high-fat diet. Hydroperoxides of cholesteryl esters and triacylglycerols were used as markers for lipoprotein lipid oxidation. Compared to controls, COQ10-treatment increased blood coenzyme Q, vitamin C, decreased blood vitamin E and had no effect on cholesterol. Also, blood from CoQ10-supplemented mice was more resistant to ex vivo lipid peroxidation. CoQ10 treatment increased coenzyme Q and vitamin E in the aorta, and decreased the absolute concentration of the lipid oxidation marker. CoQ10 treatment significantly decreased lesion size in the ascending and descending aorta. Together, this shows that CoQ10 decreases the concentration of the lipid oxidation marker in the aorta and of atherosclerosis in mice.

FREE RADICAL BIOLOGY AND MEDICINE, 2000, Vol 29, Iss 3-4, Sp. Iss. SI, pp 295-305


5. Curcumin prevents radiation-induced breast cancer

A study evaluated the preventive effect of curcumin on breast cancer tumors, which were induced by radiation in rats. Mated rats were divided into two groups at day 11 of pregnancy. The control group was fed a basal diet, and the experimental group a diet containing 1% curcumin between days 11 to 23 of pregnancy. They were implanted with a synthetic estrogen pellet. The results showed a high incidence (70%) of the development of breast tumors in the control group. However, in the rats fed curcumin, the appearance of tumors was significantly reduced to 19%. In addition, the appearance of the first tumor was delayed by 6 months in the curcumin-fed group. The average latent period until the appearance of tumors was 2.5 months longer in the curcumin-fed group. The proportion of cancer from cell walls of breast gland (17%) in total tumors in the curcumin-fed rats was decreased to half that (32%) in the controls. The blood concentrations of fatty acids, TBARS (a stress marker) and ovarian and pituitary hormones, remained the same at the control group level. There was no toxicity from curcumin, and no change in litter size and body weight of pups born from curcumin-fed rats. The results suggest that curcumin is effective as a chemopreventive treatment at the radiation-induced initiation stage of breast cancer development and does not have any side-effects.

CARCINOGENESIS, 2000, Vol 21, Iss 10, pp 1835-1841


6. Curcumin modulates tumor remission

Curcumin, the yellow pigment from the curcuma longa plant, has been shown to destroy tumors. Studies have shown that curcumin induces apoptosis (cell death) in rat macrophages (immune system cells), which leads to the inhibition of tumor growth in the body. The study suggested that the macrophages and natural killer cells play an important modulatory role in the remission of tumors. The study revealed that curcumin activates macrophages and natural killer cells (NK) during the spontaneous regression of transplanted tumors. Prolonged treatment with curcumin culminated in a stronger tumor-killing effect.

FEBS LETTERS, 2000, Vol 483, Iss 1, pp 78-82


7. Vitamin D3 vs. colon cancer?

Studies have shown that a vitamin D3 analog (F-6-D-3) significantly reduces the frequency of benign colon tumors and completely stops the development of artificially induced colon cancer in rats. Vitamin D3 inhibited the proliferation in the G1 phase of the cell cycle (synthesis and growth) of human colon cancer cells by increasing their doubling times. The mechanism by which vitamin D3 arrests the colon cancer cells is by decreasing the activity of cyclin-dependent kinase (cdk) inhibitor proteins, which decreased the activity of enzymes, kinase 2 and kinase 6. Therefore, if the antiproliferative action in the colon cancer cells of rats also occurs in tissue lining the human colon, this vitamin D3 analog may prove to have chemopreventive potential against human colon cancer, as well.

ENDOCRINOLOGY, 2000, Vol 141, Iss 11, pp 3931-3939


8. Curcumin and vitamin C inhibit free radicals

Two naturally occurring antioxidants, curcumin and vitamin C, were effective in inhibiting formation of various industrial chemicals such as hexanal when fermented cucumber tissue were exposed to oxygen. The addition of vitamin C prevented formation of most of these oxidative aldehydes at 175 ppm or greater. Curcumin, which is used commercially as a-yellow coloring in cucumber pickle products, was found to almost completely prevent aldehyde formation at 40 ppm.

JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2000, Vol 48, Iss 10, pp 4910-4912


9. Vitamin C and stomach cancer

Intestinal metaplasia (change of cells to abnormal form) plays a role in the development of intestinal gastric cancer. Vitamin C demonstrates a protective effect against gastric cancer development, due to its ability to inactivate oxygen free-radicals as well as its nitrite-scavenging effects. A study determined if long-term use of vitamin C following the eradication of Helicobacter pylori bacteria causes the regression of intestinal metaplasia in the stomach. Sixty five individuals received 500 mg of vitamin C for 6 months; the control group received none. Results in 6 months showed that in 9 of 29 (31%) individuals from the vitamin C group, there was no evidence of intestinal metaplasia in the gastric mucosa, compared to 1 of 29 (3%) from the control group. Six (20%) from the vitamin C group, who had widespread intestinal metaplasia at the start, showed less extensive inflammation with intestinal metaplasia than controls. This result was only seen in one individual from the control group. Thus, vitamin C significantly helps to resolve abnormal cell development in the stomach following the eradication of H. pylori bacteria. Its use as a chemoprevention treatment should be considered.

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, 2000, Vol 14, Iss 10, pp 1303-1309


10. Silibinin inhibits proliferation of prostate cancer cells

Silibinin, a naturally occurring flavonoid antioxidant found in the milk thistle, has recently been shown to have potent antiproliferative effects against various malignant cancer cells. A study investigated the effect of silibinin on androgen-independent prostate cancer cells. At silibinin concentrations of 0.02-20 muM, there was an increased insulin-like growth factor-binding protein 3 (IGFBP-3) accumulation in cancer cell culture. (IGFBP-3 is a protein that binds insulin-like growth factors [somatomedins], and thereby modulates/limits cell growth and metabolic actions at the cellular level. Somatomedins mediate the effect of growth hormone, secreted by the pituitary gland). There was also a dose-dependent increase of IGFBP-3 mRNA with a 9-fold increase over the starting point (at 20 muM silibinin concentration). Silibinin showed an inhibitory effect on the insulin-like growth factor I receptor-mediated signaling pathway. The results suggest a new mechanism by which silibinin inhibits cell proliferation. This justifies further investigation of the potential use of silibinin in prostate cancer treatment and prevention.

CANCER RESEARCH, 2000, Vol 60, Iss 20, pp 5617-5620


11. Curcumin may inhibit inflammation/blood clots

Curcumin is a naturally occurring polyphenolic phytochemical from the stem of the plant Curcuma longa. It possesses anti-inflammatory properties and inhibits cancer formation in mice. Many lipoxygenase inhibitors including curcumin are currently being studied for their anti-carcinogenic properties. (Lipoxygenase is an enzyme that modulates the conversion of arachidonic acid. It is the precursor for the creation of prostaglandins, thromboxanes and leukotrienes, which can cause complications such as inflammation and blood clots). Understanding how curcumin inhibits lipoxygenase may help in the development of novel anti-cancer drugs used for treatment where lipoxygenases are involved.

INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE, 2000, Vol 6, Iss 5, pp 521-526



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