An article featured in the December 15, 2009 issue of the journal Cancer Research reveals the discovery of a team at Children's Hospital & Research Center in Oakland, California of compounds occurring in soy that could help prevent and possibly treat colon cancer.
Children's Hospital Oakland Research Institute Cancer Center director Julie Saba, MD, PhD and her associates discovered that natural lipid molecules called sphingadienes may be responsible for some of the cancer-preventive benefits found for soy products. They first identified the compounds in fruit flies and found that they had the effect of inducing the death of mutant cells. The molecules were determined to be similar to sphingadienes that occur in soy sphingolipids.
When the researchers compared the effects of sphingadienes from flies or soy with those of another soy compound in experiments with cultured human colon cancer cells, sphingadienes were demonstrated to reduce cell viability dose and time-dependently by increasing apoptosis (programmed cell death) and autophagy, while the other soy compound was less effective. Nonmalignant human colon cells were shown to be less sensitive to sphingadienes' effects. In another experiment utilizing a mouse model of intestinal tumorigenesis, animals given sphingadienes averaged 35 percent fewer polyps (benign colon tumors that can become cancerous in humans), and polyps tended to be smaller compared to those detected in untreated animals.
"It's very exciting," enthused Dr Saba. "First, we are encouraged to find a natural molecule that could be consumed through soy products as a strategy to help prevent colon cancer. Second, this information is important because we can build on our understanding of the structure and metabolism of sphingadienes in terms of developing new drugs to treat people who already have colon cancer. Uncovering how sphingadienes exert their effects also helps us to find the most likely combinations of drugs that may work synergistically to eliminate cancer cells and mutant cells that could give rise to cancer."
"I would be comfortable recommending soy products as a change in the diet that could protect against cancer," she added. "The more that soy is studied, the more of these protective agents are found, so it's a very healthy diet choice."
Cancer of the colon and rectum (colorectal cancer) affects nearly 160,000 Americans each year, causing approximately 62,070 deaths annually. Colorectal cancer ranks fourth worldwide in cancer occurrence and deaths (Shibuya K et al 2002), though it has a better prognosis than do most cancers. In the general population, the risk of developing colorectal cancer is approximately 19 percent, and it is estimated that 2 percent to 5 percent of sporadic polyps will develop into an invasive cancer (Markowitz AJ et al 1997). Therefore, early detection of colorectal cancer dramatically increases survival (Weir HK et al 2003). For example, 90 percent of patients who receive treatment before the cancer has spread are alive after five years, compared to only 10 percent who survive if the cancer is widespread and treated conventionally (Dashwood RH 1999).
Ras gene mutations occur in 21 percent to 60 percent of primary colorectal cancers (Wang JY et al 2003) and contribute to tumor initiation and progression (Pretlow TP et al. 2005); thus, they may be of clinical value in the prognosis of colorectal cancer (Castagnola P et al. 2005); Okulczyk B et al 2003). K-ras mutations increase gastrin gene levels in colon cancer cells, which stimulate cell growth in some colorectal cancers (Hori H et al 2003). Furthermore, K-ras gene increases VEGF levels and thus may increase tumor angiogenesis (Zhong SS et al 2003).
Unfortunately, clinical trials using drugs that target Ras—such as tipifarnib, a farnesyl transferase inhibitor (FTI)—have been disappointing even in patients whose tumors harbor Ras mutations (Mesa RA 2006; Rao S et al. 2004). However, Ras gene activity can be slowed by:
Omega-3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) from fish oil ((Collett ED et al. 2001; Singh J et al. 1998)
d-Limonene and perillyl alcohol from citrus fruits and essential oils (Broitman SA et al. 1995; Gelb MH et al. 1995)
Epigallocatechin gallate (EGCG) from green tea extract (Lyn-Cook BD et al. 1999)
Black tea polyphenol (BTP) from black tea extract (Lyn-Cook BD et al. 1999)
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