Resveratrol Fights Multiple Myeloma
A study published in the November 1 2005 issue of the journal Cancer
Research http://cancerres.aacrjournals.org/ revealed that resveratrol, a
compound found in grapes and other plants, inhibits the growth of myeloma
cells. Multiple myeloma is an incurable cancer of the bone marrow
characterized by the accumulation of malignant plasma cells in the bone
marrow cavity. This leads to increased destruction of bone by specialized
cells called osteoclasts as well as a reduction in the formation of new bone
by cells called osteoblasts. The bone resorption caused by the disease
promotes the growth of the cancerous cells, leading to a cycle of increased
bone loss and disease progression.
Acting on the knowledge that resveratrol has been reported to inhibit
proliferation and induce apoptosis in several human cancer cell lines,
researchers in Denmark sought to determine its effects on myeloma as well as
the bone cells affected by the disease. In the current study, the
researchers treated two myeloma cell lines with increasing concentrations of
resveratrol. After two to three days, untreated cell lines had a 3 to 4 fold
increase in total cell metabolic activity, indicating a high proliferation
rate. Treatment with resveratrol dose-dependently decreased the number of
living myeloma cells via programmed cell death beginning with the second day
of treatment. After three days, the highest concentration of resveratrol
tested on the cells lowered their metabolic activity to less than that
measured at the beginning of the study, demonstrating that a high
concentration of the compound can completely prevent myeloma cell growth in
vitro.
Further experiments showed that resveratrol inhibited osteoclast
differentiation as well as bone resorption while increasing the expression
of osteoblast markers and stimulating their response to 1,25(OH) vitamin D3.
Resveratrol also was shown to stimulate the vitamin D3 receptor in
osteoblast precursors.
The authors remark that the intake of resveratrol obtained by daily moderate
wine consumption is probably too low to induce the effects observed in the
current in vitro experiments, yet they note that doses as high as 20
milligrams per kilogram resveratrol has been administered to rats for a one
month period without harm, while providing cancer preventive and/or
antitumor activities. They mention that "the gain of interest for
resveratrol for cancer treatment has encouraged the design and synthesis of
resveratrol derivatives more stable and 100-fold more potent than the native
molecule in inhibiting proliferation and inducing apoptosis in cancer cell
lines," and express their interest in determining whether these compounds
would have a similar effect on bone cells.
Protocol
Cancer adjuvant therapy
Resveratrol is one of a group of compounds (called phytoalexins) that are
produced in plants during times of environmental stress, such as adverse
weather or insect, animal, or pathogenic attack. Resveratrol has been
identified in more than 70 species of plants, including mulberries and
peanuts, and the skins of red grapes, which are a particularly rich source
(Jang et al. 1999). According to Pezzuto, "Of all the plants we’ve tested
for cancer chemopreventive activity, this one [resveratrol] has the greatest
promise" (Pezzuto 1997).
Resveratrol was effective against cancer during all three phases of the
cancer process: initiation, promotion, and progression. For example,
resveratrol displayed antimutagenic and antioxidant activity, providing
greater protection against DNA damage than vitamins C, E, or beta-carotene.
Resveratrol restored glutathione levels, considered by some as the most
essential of antioxidants (Jang et al. 1999). It increased levels of a Phase
II detoxifying enzyme (quinone reductase), an enzyme responsible for
metabolically disassembling carcinogens.
Resveratrol inhibited the activity of cyclooxygenase-2 (COX-2), reducing the
inflammatory response in human epithelial cells (Subbaramaiah et al. 1999).
Upregulation of COX-2 is associated with the physical manifestations of
various human cancers, as well as other inflammatory disorders. Since
inflammation is closely linked to tumor promotion, substances with potent
anti-inflammatory activities are thought to exert chemopreventive effects,
particularly in the promotion stage of the disease.
Resveratrol prompted differentiation of human promyelocytic leukemia cells.
The development of preneoplastic lesions in mouse mammary glands was
inhibited by resveratrol (Kang et al. 2003; Asou et al 2002; Tsan et al.
2002).
Source : LifeExtension.com
