Viagra may reduce colorectal cancer risk by half – Report

Viagra cut in half the formation of precancerous polyps that form before the onset of colorectal cancer, says cancer researcher Darren D. Browning Ph.D. – a Professor in the Department of Biochemistry & Molecular Biology and Director of the Biochemistry and Cancer Biology Graduate Program at the Medical College of Georgia (MCG) in Augusta.

The next steps should be a clinical trial for the drug in those at high risk of colorectal cancer, adds Dr. Browning, corresponding author of the study published in the journal Cancer Prevention Research.

Browning found that Viagra placed in the drinking water reduced precancerous polyps in mice. Dr. Browning’s team used mice purposely engineered with the same genetic mutation that causes humans to produce hundreds of polyps and essentially always resulting in colorectal cancer.

Viagra (sildenafil) has been used for years in a wide range of uses, from premature infants with pulmonary hypertension to an older adult with erectile dysfunction, Browning notes. The low doses of Viagra used people have no known side effects, Dr. Browning adds.

Colorectal cancer is the third leading cause of cancer death. More than 135,000 Americans will be diagnosed with the disease, and around 50,000 will die each year in the US, according to the latest data from the Surveillance, Epidemiology, and End Results (SEER) Program of the National Cancer Institute (NCI). The metastatic form of the disease is usually lethal because treatments are usually not effective after the tumor has spread.

Detecting and treating colorectal cancer in its early stages offers the best odds of survival, according to the NCI. Researchers are working on better ways to detect colorectal cancer early, developing things such as the new liquid biopsy tests, however, they haven’t been vetted in clinical trials.

One of the best ways to avoid dying from colorectal cancer is to avoid getting the disease in the first place or detecting the disease early using existing screening tests. According to the CDC, screening for colorectal cancers as recommended helps prevent the disease by finding precancerous lesions so they can be treated before they become cancerous. Screening for colorectal cancer also helps find this disease at an early stage, when treatment works best. The CDC offers free or low-cost colorectal cancer screening in six states.

How Viagra Prevents Colorectal Cancer

Viagra relaxes the smooth muscle cells around blood vessels so they can more easily fill with blood, which is how it helps both pulmonary hypertension and erectile dysfunction. As well, Dr. Browning’s lab showed that the drug also increases levels of cyclic GMP, a chemical known to affect the intestinal lining, referred to as the epithelium.

Dr. Browning and his team observed that increased cyclic GMP had a multitude of other effects, including suppressing some excessive cell proliferation that occurs in the gut and increasing normal cell differentiation and eliminating abnormal cells through a process of programmed cell death called apoptosis.

Existing polyps were not affected, more evidence that targeting cyclic GMP signaling appears to be a good prevention strategy in high-risk patients, Browning adds.

Viagra inhibits PDE5, an enzyme found in colon cells and other tissues that breaks down cyclic GMP.  In turn, this makes more cyclic GMP available to reduce cell proliferation and improve differentiation into the types of cells that secrete protective mucus.

The mice used in Browning’s study had mutations in the APC gene, a known tumor suppressor. Just like these mice, humans with APC mutations can develop hundreds of polyps in the rectum and colon and are considered at highest risk for colorectal cancer, says Dr. Browning, describing the inherited disorder called familial adenomatous polyposis (FAP). According to the National Institutes of Health, people with the classic form of FAP develop colon cancer at the average age of 39.

Browning points out that about 80 percent of colorectal cancers form spontaneously when cells in this high-cell turnover area divide and through DNA damage, develop a mutation that can support uncontrolled proliferation. Although scientists don’t know all of the exact causes of colorectal cancer, mutations occur more often when we consume carcinogens such as those found in processed or over-cooked meats.  These carcinogens give rise to free radicals which damage DNA.

The researchers in this study evaluated the risk of developing colorectal cancer associated with a gene mutation called adenomatous polyposis coli (APC) among mice who were given Viagra. APC is a tumor suppressor, so individuals with an APC genetic mutation may develop scores of colorectal polyps, which have the potential to develop into cancer.

In this study, the investigators, under direction of cancer researcher Dr. Darren D. Browning of the Georgia Cancer Center and the Department of Biochemistry and Molecular Biology at Augusta University, learned that a low dose of sildenafil taken daily by mice who had been genetically modified to develop colorectal polyps caused a rise in levels of cyclic guanosine monophosphate (cGMP).

Reference – Augusta University

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