Abstract
Abstract Tetraiodothyroacetic acid (tetrac) and its nanoparticulate derivative (Nano-diamino-tetrac, NDAT) inhibit cancer cell proliferation by multiple mechanisms. Resveratrol causes inducible COX-2-dependent antiproliferation in multiple types of cancer cells. Both agents suppress tumorigenesis in xenograft models. In the current study, we demonstrated the potentiating effect of NDAT on resveratrol-induced antiproliferation in human colorectal cancer cells. Induction of antiproliferation by resveratrol was shown by induction of COX-2, by increased expression of of antiproliferative genes and by reduction of transcription of pro-proliferative genes. Antiproliferation induced by NDAT was associated with downregulation of ribonucleoside-diphosphate reductase subunit 2 (RRM2), an inhibitor of resveratrol-induced COX-2 accumulation. Interestingly, resveratrol itself induced RRM2 expression in a concentration-dependent manner that was variable among different colorectal cancer cells. Knockdown of RRM2 by shRNA increased resveratrol-induced COX-2 expression. Combined treatment with resveratrol and NDAT in shRNA-transfected colorectal cancer cells resulted in further enhancement of COX-2 accumulation and antiproliferation. In summary, RRM2 is a target of NDAT and may contribute to increased resveratrol-induced antiproliferation in colorectal cancer cells in the presence of NDAT. From these studies, we expect to develop a cellular and molecular mechanistic framework for better delineation of the chemotherapeutic activities of NDAT with resveratrol against colorectal carcinogenesis. Novel biomarkers may also emerge from such studies. Citation Format: Yu-Tang Chin, Chi-Yu Lin, Ya-Jung Shih, Shin-Ying Lin, YiRu Chen, Shaker A. Mousa, Heng-Yun Tang, Hung-Yun Lin, Paul J. Davis. Nano-diamino-tetrac (NDAT) enhances resveratrol-induced antiproliferation by reducing RRM2 expression in colorectal cancer cells [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2017 Oct 26-30; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2018;17(1 Suppl):Abstract nr A196.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
