| Kinase Assay: |
| Cancers, 2019,11(3):427. | | The Flavonoid Metabolite 2,4,6-Trihydroxybenzoic Acid Is a CDK Inhibitor and an Anti-Proliferative Agent: A Potential Role in Cancer Prevention.[Reference: WebLink] | Flavonoids have emerged as promising compounds capable of preventing colorectal cancer (CRC) due to their anti-oxidant and anti-inflammatory properties. It is hypothesized that the metabolites of flavonoids are primarily responsible for the observed anti-cancer effects owing to the unstable nature of the parent compounds and their degradation by colonic microflora.
METHODS AND RESULTS:
In this study, we investigated the ability of one metabolite, 2,4,6-Trihydroxybenzoic acid (2,4,6-THBA) to inhibit Cyclin Dependent Kinase (CDK) activity and cancer cell proliferation. Using in vitro kinase assays, we 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. Interestingly, no significant CDK inhibition was observed with the structurally related compounds 3,4,5-trihydroxybenzoic acid (3,4,5-THBA) and phloroglucinol, suggesting that 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. Consistent with this, in cells expressing functional SLC5A8, 2,4,6-THBA induced CDK inhibitory proteins p21Cip1 and p27Kip1 and inhibited cell proliferation.
CONCLUSIONS:
These findings, for the first time, suggest that the flavonoid metabolite 2,4,6-THBA may mediate its effects through a CDK- and SLC5A8-dependent pathway contributing to the prevention of CRC. |
|
| Structure Identification: |
| China Journal of Chinese Materia Medica, 2001, 26(4):260-262. | | Studies on chemical constitutents from Penthorum chinense Pursh.[Reference: WebLink] | To study the chemical constituents of Penthorum chinense.
METHODS AND RESULTS:
Silica gel and macroporous resin were used as adsorbent for isolation and purification. The chemical structures were elucidated by spectral analysis and chemical methods.Three compounds were isolated from the water-extract of P. chinense. The structures were identified as 5-hydroxy-flavanone-7-O-β-D-glucoside (Ⅰ), 2,4,6-Trihydroxybenzoic acid (Ⅱ) and quercetin(Ⅲ), respectively.
CONCLUSIONS:
Compounds Ⅰ and Ⅱ were isolated from this plant for the first time. |
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