Life Extension Update
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.
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).
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