Nano-Diamino-Tetrac (NDAT) Enhances Resveratrol-Induced Antiproliferation by Action on the RRM2 Pathway in Colorectal Cancers

Hormones & Cancer
André Wendindondé NanaHung-Yun Lin

Abstract

Cancer resistance to chemotherapeutic agents is a major issue in the management of cancer patients. Overexpression of the ribonucleotide reductase regulatory subunit M2 (RRM2) has been associated with aggressive cancer behavior and chemoresistance. Nano-diamino-tetrac (NDAT) is a nanoparticulate derivative of tetraiodothyroacetic acid (tetrac), which exerts anticancer properties via several mechanisms and downregulates RRM2 gene expression in cancer cells. Resveratrol is a stilbenoid phytoalexin which binds to a specific site on the cell surface integrin αvβ3 to trigger cancer cell death via nuclear translocation of COX-2. Here we report that resveratrol paradoxically activates RRM2 gene expression and protein translation in colon cancer cells. This unanticipated effect inhibits resveratrol-induced COX-2 nuclear accumulation. RRM2 downregulation, whether achieved by RNA interference or treatment with NDAT, enhanced resveratrol-induced COX-2 gene expression and nuclear uptake which is essential to integrin αvβ3-mediated-resveratrol-induced antiproliferation in cancer cells. Elsewhere, NDAT downregulated resveratrol-induced RRM2 expression in vivo but potentiated the anticancer effect of the stilbene. These findings suggest that ...Continue Reading

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Citations

Sep 24, 2019·Frontiers in Endocrinology·Fabio GionfraSandra Incerpi
Mar 28, 2019·Frontiers in Endocrinology·Yu-Tang ChinJacqueline Whang-Peng
Jul 25, 2019·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Yi-Ru ChenKuan Wang
Nov 24, 2020·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yaqiong ZhanYunqing Qiu
Dec 31, 2019·Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association·Yih HoKuan Wang
Apr 9, 2021·Journal of Biomedical Science·Yu-Chen S H YangKuan Wang

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