News Source: Health Day News
Fish Oil Might Slow Prostate Cancer
Early study with mice suggests a potentially beneficial effect
By E.J. Mundell
HealthDay Reporter
THURSDAY, June 21 (HealthDay News) -- A new study with mice suggests that diets high in omega-3 fatty acids from fish might help slow prostate cancer.
The comparable levels of dietary omega-3s used in the study "are much higher than the average Western diet, but they are not unachievable," said senior researcher Yong Chen, a professor of cancer biology at Wake Forest University School of Medicine in Winston-Salem, N.C.
Omega-3 fatty acids -- especially the "long-chain" forms found in oily fish -- have become the latest nutrition superstars, with studies suggesting they can help prevent heart disease and even cancer.
The exact mechanism driving the purported anti-cancer effect is still unclear, Chen said. One leading theory contends that specific cellular enzymes metabolize omega-3s in ways that retard malignancy.
However, Chen's team is investigating a much lesser-known mechanism.
"It turns out that [long-chain] omega-3 fatty acids might modulate apoptosis -- a form of cell death," he said.
Cancer cells spread in two ways: either they proliferate uncontrollably, or they bypass natural signaling that tells them to commit suicide, or apoptosis.
"It turns out that a key molecule -- that happens to be called 'Bad' -- may be involved in this process," Chen said. His team now believes that long-chain omega-3s interact favorably with Bad to push cancer cells back into a normal apoptosis.
In their study, the researchers fed mice diets high in both omega-3 fatty acid and the less-healthy omega-6 fatty acids. These mice were genetically engineered to lack the Pten tumor suppressor gene, leaving them highly prone to prostate tumors. Dysfunctional Pten plays a key role in about one-third of human prostate cancers, so this mouse is a great model for human disease, Chen said.
As expected, mice with functioning Pten did not develop prostate cancer, the researchers said.
On the other hand, rodents whose Pten was switched off typically developed prostate tumors. However, 60 percent of these mice survived if they were fed a high omega-3 diet, compared to just 10 percent given a low omega-3 diet. None of the mice given the high omega-6 diet survived, the team noted.
There was another wrinkle to the study. In the past, it has been tough for researchers to tease out the effects of omega-6 and omega-3 fatty acids, which usually occur together in foods. But Chen's team introduced another gene into the Pten-less mice. This gene caused the mice to convert omega-6 fatty acids into the omega-3 form, thereby limiting this confounding factor.
"That's really a big strength of this study; nobody had really ever done that before," Chen said.
The study is published June 21 in the online edition of the Journal of Clinical Investigation.
According to Chen, the study suggests that diets high in long-chain omega-3 fatty acids might give men an edge against prostate cancer.
But not everyone is convinced.
"Recent large reviews and meta-analyses tend to suggest no major effects of fish [intake] on cancer risk," said Paul Terry, assistant professor in the department of epidemiology at the Emory University School of Public Health, in Atlanta.
"The fact that they [the Wake Forest researchers] identified and addressed another potential mechanism in their study is certainly helpful," he added. However, he said, "how this mechanism relates to the many others identified and shown in studies to be possibly important remains unclear."
Terry said rodent studies can only tell scientists so much, and "clinical trials in humans of long-chain omega-3 fatty acids and tumor characteristics, for example, are relatively scarce. This study, and others, provides some more rationale for conducting such trials."
For his part, Chen said it's important that consumers realize that not all omega-3s are created equal in terms of their potential health benefits.
"In this study, we are only referring to the long-chain form" found in oily fish, such as mackerel, herring, albacore tuna and salmon, he said. Other, shorter-chain varieties can be found in flaxseed and plant sources, but their impact, if any, on cancer is even less clear.
"We are doing a type of study right now to see whether there is any difference," Chen said.
More information
There's more on omega-3 fatty acids and cancer at the American Cancer Society:
http://www.cancer.or...Fatty_Acids.asp
SOURCES: Yong Q. Chen, Ph.D., professor, cancer biology, Wake Forest University School of Medicine, Winston-Salem, N.C.; Paul Terry, Ph.D., assistant professor, department of epidemiology, Emory University School of Public Health, Atlanta; June 21, 2007, Journal of Clinical Investigation, online
Copyright © 2007 ScoutNews, LLC. All rights reserved.
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Here is the study abstract:
J. Clin. Invest. doi:10.1172/JCI31494.
Copyright ©2007 by the American Society for Clinical Investigation
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Online First Publication
Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids
Isabelle M. Berquin1,2, Younong Min1, Ruping Wu1, Jiansheng Wu1, Donna Perry2, J. Mark Cline2, Mike J. Thomas3, Todd Thornburg4, George Kulik1, Adrienne Smith1, Iris J. Edwards2, Ralph D’Agostino, Jr.5, Hao Zhang6, Hong Wu7, Jing X. Kang8 and Yong Q. Chen1,4
1Department of Cancer Biology, 2Department of Pathology, 3Department of Biochemistry, 4Comprehensive Cancer Center, and 5Department of Biostatistical Science, Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA. 6Laboratory of Food Biotechnology, School of Food Science and Technology, Southern Yangtze University, Wuxi, People’s Republic of China. 7Department of Molecular and Medical Pharmacology, UCLA David Geffen School of Medicine, Los Angeles, California, USA. 8Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Address correspondence to: Yong Q. Chen, Wake Forest University School of Medicine, Medical Center Boulevard, Winston-Salem, North Carolina 27157, USA. Phone: (336) 713-7655; Fax: (336) 713-7660; E-mail: yqchen@wfubmc.edu.
Received for publication January 12, 2007, and accepted in revised form April 24, 2007.
Although a causal role of genetic alterations in human cancer is well established, it is still unclear whether dietary fat can modulate cancer risk in a predisposed population. Epidemiological studies suggest that diets rich in omega-3 polyunsaturated fatty acids reduce cancer incidence. To determine the influence of fatty acids on prostate cancer risk in animals with a defined genetic lesion, we used prostate-specific Pten-knockout mice, an immune-competent, orthotopic prostate cancer model, and diets with defined polyunsaturated fatty acid levels. We found that omega-3 fatty acids reduced prostate tumor growth, slowed histopathological progression, and increased survival, whereas omega-6 fatty acids had opposite effects. Introducing an omega-3 desaturase, which converts omega-6 to omega-3 fatty acids, into the Pten-knockout mice reduced tumor growth similarly to the omega-3 diet. Tumors from mice on the omega-3 diet had lower proportions of phosphorylated Bad and higher apoptotic indexes compared with those from mice on omega-6 diet. Knockdown of Bad eliminated omega-3–induced cell death, and introduction of exogenous Bad restored the sensitivity to omega-3 fatty acids. Our data suggest that modulation of prostate cancer development by polyunsaturated fatty acids is mediated in part through Bad-dependent apoptosis. This study highlights the importance of gene-diet interactions in prostate cancer.
Copyright © 2007 by the American Society for Clinical Investigation.
