In:
Molecular Cancer Therapeutics, American Association for Cancer Research (AACR), Vol. 17, No. 1_Supplement ( 2018-01-01), p. A196-A196
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.
Type of Medium:
Online Resource
ISSN:
1535-7163
,
1538-8514
DOI:
10.1158/1535-7163.TARG-17-A196
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2018
detail.hit.zdb_id:
2062135-8
SSG:
12
Bookmarklink