Vitamin D may be crucial in preventing colon cancer

May 16, 2002

New studies by researchers at the Howard Hughes Medical Institute indicate that vitamin D protects against colon cancer by helping to detoxify cancer-triggering chemicals that are released during the digestion of high-fat foods.

The discovery, which was made by a team of researchers that included Howard Hughes Medical Institute (HHMI) investigators David J. Mangelsdorf at the University of Texas Southwestern Medical Center and Ronald M. Evans of The Salk Institute and colleagues at the University of Arizona, was reported in the May 17, 2002, issue of the journal Science.

The studies show that a specific type of bile acid, called lithocholic acid (LCA), which is a known carcinogen, activates the vitamin D receptor. When the vitamin D receptor is switched on, it triggers other proteins that detoxify the bile acid.

The research suggests that a drug that acts like vitamin D might help in preventing colon cancer by turning on the vitamin D receptor and clearing LCA from the body. One obstacle that must be overcome, however, is that high intake of vitamin D or drugs that mimic vitamin D can lead to dangerous levels of calcium in the blood.

Colon cancer expert Bert Vogelstein, an HHMI investigator at the Sidney Kimmel Comprehensive Cancer Center at The Johns Hopkins University, said, "these studies provide important new clues to the relationship between vitamin D, bile acids, and colorectal cancer, and they have significant implications for colorectal cancer prevention in the future."

Mangelsdorf, Evans and their colleagues studied the effects of the bile acid, LCA, which is produced as a by-product when intestinal bacteria digest primary bile acids produced in the liver. Primary bile acids help the body digest dietary fats. The experiments showed that LCA activates the vitamin D receptor, which then activates additional genes that help detoxify LCA.

"There's an abundance of epidemiologic data, as well as some scientific data, suggesting a correlation between high-fat diets, bile acids such as LCA, and colon cancer," said Mangelsdorf. "But there has been no causal link, which has been one of the frustrating aspects of trying to understand the relationship between our Western-style high-fat diet and colon cancer.

Although it had been shown that vitamin D can prevent colon cancer in rats treated with LCA, and that humans with defective vitamin D signaling pathways have a higher incidence of colon cancer, it remained unclear how vitamin D actually prevents colon cancer. A reasonable theory, according to Mangelsdorf, was that vitamin D and LCA both triggered a biochemical pathway involved in detoxifying LCA. The best candidate was a pathway that involved the vitamin D receptor.

In one set of studies, the researchers showed that the vitamin D receptor strongly binds to LCA. But the researchers also needed to demonstrate that binding LCA actually activates a key gene, called CYP3A, which triggers the cell's detoxification machinery. The scientists attached a "reporter" gene to CYP3A in human cells in culture, so they could detect whether the CYP3A gene was switched on when LCA attached to the vitamin D receptor.

"Other investigators had published data showing that vitamin D could switch on this gene, but it was a big surprise that LCA could do it also," said Mangelsdorf. The scientists also performed experiments in mice, in which they found that feeding the animals LCA led to the activation of certain vitamin-D-receptor target genes.

The scientists ultimately demonstrated that the vitamin D receptor was the only receptor activated by LCA. "We showed that in our knockout mice, LCA still induces the expression of CYP3A, just like vitamin D does," said Mangelsdorf. "So this crucial experiment demonstrated that vitamin D and LCA were not working through another receptor but through the vitamin D receptor."

According to Mangelsdorf, the findings suggest that the vitamin D receptor acts as a sensor for the toxic chemical LCA. Other receptors in the body can sense dietary fats and other foreign chemicals, and serve to "alert" the body to begin detoxification when the chemicals reach dangerous levels.

"Our findings suggest a new look at the relationship between nutrition and cancer, particularly how vitamin D protects against colon cancer," he said. "One problem with using vitamin D as a protective drug has always been that it produces hypercalcemia. But now we know that there's another endogenous compound, LCA, that can also attach to the receptor, this suggests that we can develop protective drugs that don't produce hypercalcemia, but do activate the detoxification pathway."
-end-


Howard Hughes Medical Institute

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.