Abstract 101: Studies on the flavonoid metabolite 2,4,6-trihydroxybenzoic acid as a CDK inhibitor and anti-proliferative agent: Potential role in cancer prevention

Abstract

Abstract Colorectal cancer (CRC) is the second highest cause of cancer deaths in the United States according to Center for Disease Control. Increasing evidences suggest that a diet rich in fruits and vegetables will reduce incidences of colorectal adenomas. We hypothesize that the natural compounds present in fruits and vegetables, along with their metabolites generated by the gut microbiota, could be responsible for cancer prevention by targeting the cell cycle proteins. Previous studies conducted in the laboratory have identified 2,4,6- Trihydroxybenzoic acid (2,4,6-THBA), one of the degradation products of flavonoids, as a potential chemo-preventive agent mediating its effect through inhibition of cyclin dependent kinases (CDKs). Transport of monocarboxylic acids like 2,4,6-THBA is mediated by the Solute Ligand Carrier (SLC) family of transporters; in particular SLC5A8 and SLC5A12 have been implicated as tumor suppressor proteins that are down-regulated/non-functional in various cancers. In this study, we investigated the ability of the monocarboxylic acid transporter SLC5A8 to transport 2,4,6-THBA into the mammalian cells. Our pilot studies show that the cells expressing SLC5A8 transporters have the capacity to transport 2,4,6-THBA leading to upregulation of p21 and p27 as measured by western blots and qPCR. This was associated with decreased cell number as well as decreased colony formation as measured through clonogenic assays. We suggest that chemo-preventive actions of dietary compounds containing flavonoids may occur through 2,4,6-THBA, contributing largely to the prevention of CRC. Citation Format: Ranjini Sankaranarayanan, Chaitanya K. Valiveti, Severine van Slambrouck, Siddharth S. Kesharwani, D. Ramesh Kumar, Teresa Seefeldt, Hemachand Tummala, Jayarama B. Gunaje. Studies on the flavonoid metabolite 2,4,6-trihydroxybenzoic acid as a CDK inhibitor and anti-proliferative agent: Potential role in cancer prevention [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 101.