Eating fruits and vegetables may help prevent colorectal cancer
USA: Eating fruits and vegetables may protect you from colorectal cancer (CRC) or colon cancer, a recent study published in the journal Cancers has implied. According to the study, flavonoids -- the natural compound present in fruits and vegetables -- can help in the prevention of colorectal cancer. The findings for the first time suggest that flavonoid metabolite 2,4,6-THBA may mediate its effects through a CDK- and SLC5A8-dependent pathway that contributes to CRC prevention.
Previous studies conducted through the last 20 years have established the link between flavonoids and the prevention of colorectal cancer, but scientists have struggled to determine how flavonoids are responsible for cancer prevention.
Ranjini Sankaranarayanan, South Dakota State University, Brookings, USA, and colleagues investigated the ability of one metabolite, 2,4,6-trihydroxy benzoic acid (2,4,6-THBA) to inhibit Cyclin-Dependent Kinase (CDK) activity and cancer cell proliferation. They demonstrated that 2,4,6-THBA dose-dependently inhibited CDKs 1, 2 and 4 and in silico studies identified key amino acids involved in these interactions using in vitro kinase assays.
Colorectal cancer, cancer of the colon or rectum, is the second leading cause of cancer-related death in men and women in the United States. According to the American Cancer Society, colorectal cancer rates among those under 50 years of age have increased by more than 50% since 1994.
Key findings of the study include:
- Using in vitro kinase assays, the researchers demonstrated that 2,4,6-THBA dose-dependently inhibited CDKs 1, 2 and 4 and in silico studies identified key amino acids involved in these interactions.
- No significant CDK inhibition was observed with the structurally related compounds 3,4,5-trihydroxy benzoic acid (3,4,5-THBA) and phloroglucinol, suggesting that the orientation of the functional groups and specific amino acid interactions may play a role in inhibition.
- We showed that cellular uptake of 2,4,6-THBA required the expression of functional SLC5A8, a monocarboxylic acid transporter.
- In cells expressing functional SLC5A8, 2,4,6-THBA induced CDK inhibitory proteins p21Cip1 and p27Kip1 and inhibited cell proliferation.
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"Our finding that 2,4,6-THBA is an effective inhibitor of CDKs that acts as an anti-proliferative agent suggests that it has the potential to be developed into a novel class of CDK inhibitors," concluded the authors.
Flavonoids decrease colorectal cancer due to the action of the degraded or broken down, products rather than the parent compounds -- such as 2,4,6-THBA. A class of flavonoids called anthocyanins give color to fruits, such as grapes, blueberries, and blackberries.
Flavonoids are relatively stable in the acidic environment of the stomach but degrade in the more alkaline intestines. Bacteria living in the colon further degrade these compounds. This process then exposes the gastrointestinal tract to these compounds in higher concentrations. 2,4,6-THBA binds to three enzymes required for cancer cell division. This may be contributing to cancer prevention.
The study, "The Flavonoid Metabolite 2,4,6-Trihydroxybenzoic Acid Is a CDK Inhibitor and an Anti-Proliferative Agent: A Potential Role in Cancer Prevention," is published in the MDPI journal Cancers.