South Dakota State University Discover Flavonoid Metabolite 2,4,6-Trihydroxybenzoic Acid That Fights Colorectal Cancer
Source: Thailand Medical News Nov 28, 2019 5 years, 3 weeks, 4 days, 2 hours, 50 minutes ago
Flavonoids which are phytochemicals found in fruits and vegetables, can help prevent colorectal cancer. Though studies conducted during the last 20 years have established this, scientists have struggled to determine how flavonoids are responsible for cancer prevention.
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Associate professor Jayarama Gunaje, left, and doctoral student Ranjini Sankaranarayanan of the Department of
Pharmaceutical Sciences . Credit: South Dakota State University
Associate Professor Dr Jayarama Gunaje from Department of Pharmaceutical Sciences and the rest of his team from South Dakota State University have discovered one of the mechanisms through which flavonoids prevent
colorectal cancer. They found that
2,4,6-trihydroxybenzoic acid, one of the compounds produced when the body metabolizes or breaks down
flavonoids, can inhibit
cancer cell growth under specific conditions.
The medical researchers are the first to explore the
cancer-inhibiting potential of
2,4,6-THBA as a metabolite produced through
flavonoid degradation. Their work was published this year in
Cancers.
Colorectal cancer (CRC) is the third most commonly diagnosed malignancy and the fourth leading cause of
cancer-related deaths in the world, and its burden is expected to increase by 60% to more than 2.2 million new cases and 1.1 million
cancer deaths by 2030. The
Colorectal Cancer Alliance estimates more than 135,000 Americans will be diagnosed with colon or rectal
cancer this year alone and more than 50,000 patients will die from
colorectal cancers this year. Furthermore,
colorectal cancer rates among those under 50 years of age have increased by more than 50% since 1994, according to the American
Cancer Society.
Dr Jayarama Gunaje told
Thailand Medical News via a phone interview, "We have so many drugs to treat
cancer, but almost none to prevent it. Therefore, demonstrating
2,4,6-THBA as a protective agent against
colorectal cancer has immense potential health benefits."
The medical researchers are now identifying the bacteria responsible for degrading
flavonoids. That may then lead to developing probiotics that can help prevent
colorectal cancer. The research project is funded through the SDSU Research and Scholarship Support Fund and the Department of Pharmaceutical Sciences.
During the process of investigating how aspirin decreases colorectal cancer, Gunaje'
s group documented that
2,4,6-THBA , a derivative of
salicylic acid, has the ability to inhibit
cancer cell growth. A search for natural sources with this
cancer-preventing compound led to focusing on the polyphenolic flavonoids.
Dr Jayarama Gunaje added, "We hypothesized that
flavonoids decrease
colorectal cancer due to the action of the degraded, or broken down, products rather than the parent compounds. These areas are underexplored. One of these products is
2,4,6-THBA.”
"Typically,the metabolite is present in red wine in small amounts," explained doctoral student Dr Ranjini Sankaranarayanan, pointing to a class of
flavonoids called
anthocyanins, which give color to fruits, such as grapes, blueberries and blackberries.
Although
flavonoids are relatively stable in the acidic environment of the stomach, they degrade in the intestines, which are more alkaline, she continued.
Bacteria living in the colon further degrade these compounds. "This process then exposes the gastrointestinal tract to these compounds in higher concentrations," Gunaje said.
Dr Sankaranarayanan confirmed 2,4,6-THBA binds to three enzymes required for
cancer cell division. "This may be contributing to
cancer prevention," Gunaje said. However, when the researchers treated
colon cancer cells with
2,4,6-THBA, it surprisingly had no effect.
Reviewing back to the literature, the researchers found that
2,4,6-THBA needs a transporter protein on the plasma membrane to enter the cell. However, Gunaje pointed out, "
cancer cells make the SLC5A8 transporter protein dysfunctional through genetic mutation, it's a protective factor for
cancer cells to grow."
The medical researchers then obtained an artificially created breast
cancer cell line that expresses the transporter protein to do further testing. Doctoral student Chaitanya Valiveti performed cell uptake studies that confirmed
2,4,6-THBA was getting inside the cells that express the transporter but had not entered the cells that did not have the transporter protein.
Dr Jayarama Gunaje added, "This proves that the transporter is required and
2,4,6-THBA has the ability to inhibit
cancer growth if the cell expresses an authentic transporter. The mechanism likely targets enzymes involved in cell division thereby inhibiting cancer cell growth.”
Dr Jayarama Gunaje explained that the
flavonoid metabolite can help prevent
cancer in two ways. First, by slowing down the rate of proliferation,
2,4,6-THBA gives T cells and natural killer cells that police the body a greater opportunity to destroy the
cancer cells. Second, when a normal cell contains damaged DNA, mutations can occur. The slowdown in cell proliferation provides time for the cells to repair their DNA, thereby preventing the accumulation of mutations.
Dr Jayarama Gunaje concluded, "
Cancer is not going away, so we need to find ways to prevent it. That is why we are excited about the discovery of
2,4,6-THBA as an inhibitor of
cancer cell growth."
Reference : Ranjini Sankaranarayanan et al. The Flavonoid Metabolite 2,4,6-Trihydroxybenzoic Acid Is a CDK Inhibitor and an Anti-Proliferative Agent: A Potential Role in Cancer Prevention, Cancers (2019). DOI: 10.3390/cancers11030427
