AI Article Synopsis
- - Nobiletin (NBT) is a flavonoid found in citrus fruits, showing potential to prevent colon cancer in rodent studies, but its specific molecular targets were previously unknown.
- - This study identifies HSC70 as a direct protein target of NBT in colon cancer cells, revealing that NBT binds to HSC70's ATP-binding site and inhibits its ATPase activity.
- - The major metabolites of NBT produced in the colon also demonstrated similar inhibitory effects on HSC70, supporting the need for further research on the role of NBT and its metabolites in cancer prevention.
Article Abstract
Nobiletin (NBT) is a unique flavonoid mainly found in citrus fruits and has been reported to inhibit colon carcinogenesis in multiple rodent models. However, the direct molecular targets of NBT are unknown, which greatly limits its utilization in cancer prevention and treatment. In this study, using affinity chromatography, proteomics, computer modeling and various biochemical analyses, for the first time we identified HSC70 as a direct protein target of NBT in colon cancer cells. Moreover, NBT bound to HSC70 at its ATP-binding site and inhibited its ATPase activity. Importantly, our results also demonstrated that the major colonic metabolites of NBT (generated in the colon of NBT-fed mice) produced similar inhibitory effects against HSC70-mediated pro-carcinogenic events to those of NBT. Overall, our results provide a solid basis to further investigate the implication of the interaction between NBT/NBT metabolites and HSC70 in cancer chemoprevention.
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| http://dx.doi.org/10.1039/d4fo03211j | DOI Listing |
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