Abstract 4411: Identification of novel natural compounds as potential inhibitors of cyclin dependent kinases

Abstract

Colorectal cancer (CRC) is the second highest cause of cancer deaths in the United States according to CDC (2017). Lifestyle factors including, but not limited to, elevated Body Mass Index (BMI), obesity and diet are proposed to lead to the development of CRC with an estimated annual incidence of 95,520 cases. 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. In this study, we investigated the ability of polyphenols [Epigallocatechin Gallate (EGCG), Catechin, Catechin Gallate (CG), and Epigallocatechin (EGC)] and their degradation products [Phloroglucinol; 2,4,6 Trihydroxybenzoic acid (2,4,6 THBA); 3,4 Dihydroxyhydrocinnamic acid (3,4-DHHCA); etc.] to inhibit the CDKs (that regulate cell cycle) activity. Our pilot studies show that the different catechin compounds and their degradation products are capable of inhibiting different CDKs, suggesting their potential role in cancer prevention. We are currently investigating the mechanism of inhibition of CDKs by these compounds utilizing biochemical and molecular docking studies. Elucidation of this pathway will suggest the role of polyphenols in the prevention of CRC as well as assist in the identification of novel compounds that can be used for both cancer prevention and therapy. Citation Format: Ranjini Sankaranarayanan, Rakesh Dachineni, Siddharth Kesharwani, Ramesh Kumar Dhandapani, Hemachand Tummala, Jayarama B. Gunaje. Identification of novel natural compounds as potential inhibitors of cyclin dependent kinases [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 4411.