Curcumin suppresses oncogenicity of human colon cancer cells by covalently modifying the cysteine 67 residue of SIRT1

Yeon Hwa Lee, Na Young Song, Jinyoung Suh, Do Hee Kim, Wonki Kim, Jihyae Ann, Jeewoo Lee, Jeong Heum Baek, Hye Kyung Na, Young Joon Surh

Research output: Contribution to journalArticlepeer-review

41 Citations (Scopus)

Abstract

SIRT1, an NAD+-dependent histone/protein deacetylase, has diverse physiological actions. Recent studies have demonstrated that SIRT1 is overexpressed in colorectal cancer, suggesting its oncogenic potential. However, the molecular mechanisms by which overexpressed SIRT1 induces the progression of colorectal cancer and its inhibition remain largely unknown. Curcumin (diferuloymethane), a major component of the spice turmeric derived from the plant Curcuma longa L., has been reported to exert chemopreventive and anti-carcinogenic effects on colon carcinogenesis. In the present study, we found that curcumin reduced the expression of SIRT1 protein without influencing its mRNA expression in human colon cancer cells, suggesting posttranslational regulation of SIRT1 by this phytochemical. Notably, ubiquitination and subsequent proteasomal degradation of SIRT1 were induced by curcumin treatment. Results of nano-LC-ESI-MS/MS revealed the direct binding of curcumin to cysteine 67 of SIRT1. In line with this result, the protein stability and clonogenicity of a mutant SIRT1 in which cysteine 67 was substituted by alanine were unaffected by curcumin. Taken together, these observations suggest that curcumin facilitates the proteasomal degradation of oncogenic SIRT1 through covalent modification of SIRT1 at the cysteine 67 residue.

Original languageEnglish
Pages (from-to)219-229
Number of pages11
JournalCancer Letters
Volume431
DOIs
Publication statusPublished - 2018 Sep 1

Bibliographical note

Funding Information:
This study was supported by the Global Core Research Center (GCRC) grant (No. 2011-0030001) from the National Research Foundation (NRF) of Republic of Korea.

Funding Information:
This study was supported by the Global Core Research Center (GCRC) grant (No. 2011-0030001 ) from the National Research Foundation (NRF) of Republic of Korea .

Publisher Copyright:
© 2018 Elsevier B.V.

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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