BCM-95® (CURCUGREEN®), 20 Mar 2011
Published on : 2015 Mar;36(3):355-67. doi: 10.1093/carcin/bgv006. Epub 2015 Feb 4.

Curcumin mediates chemosensitization to 5-fluorouracil through miRNA-induced suppression of epithelial-to-mesenchymal transition in chemoresistant colorectal cancer

Shusuke Toden , Yoshinaga Okugawa , Thomas Jascur , Dominik Wodarz , Natalia L Komarova , Constanze Buhrmann , Mehdi Shakibaei , C Richard Boland , Ajay Goel

PMID: 25653233 PMCID: PMC4400529 DOI: 10.1093/carcin/bgv006


Resistance to cytotoxic chemotherapy is a major cause of mortality in colorectal cancer (CRC) patients. Chemoresistance has been linked primarily to a subset of cancer cells undergoing epithelial-mesenchymal transition (EMT). Curcumin, a botanical with antitumorigenic properties, has been shown to enhance sensitivity of cancer cells to chemotherapeutic drugs, but the molecular mechanisms underlying this phenomenon remain unclear. Effects of curcumin and 5-fluorouracil (5FU) individually, and in combination, were examined in parental and 5FU resistant (5FUR) cell lines. We performed a series of growth proliferation and apoptosis assays in 2D and 3D cell cultures. Furthermore, we identified and analyzed the expression pattern of a subset of putative EMT-suppressive microRNAs (miRNAs) and their downstream target genes regulated by curcumin. Chemosensitizing effects of curcumin were validated in a xenograft mouse model. Combined treatment with curcumin and 5FU enhanced cellular apoptosis and inhibited proliferation in both parental and 5FUR cells, whereas 5FU alone was ineffective in 5FUR cells. A group of EMT-suppressive miRNAs were upregulated by curcumin treatment in 5FUR cells. Curcumin suppressed EMT in 5FUR cells by downregulating BMI1, SUZ12 and EZH2 transcripts, key mediators of cancer stemness-related polycomb repressive complex subunits. Using a xenograft and mathematical models, we further demonstrated that curcumin sensitized 5FU to suppress tumor growth. We provide novel mechanistic evidence for curcumin-mediated sensitization to 5FU-related chemoresistance through suppression of EMT in 5FUR cells via upregulation of EMT-suppressive miRNAs. This study highlights the potential therapeutic usefulness of curcumin as an adjunct in patients with chemoresistant advanced CRC.

© The Author 2015. Published by Oxford University Press. All rights reserved.

https://pubmed.ncbi.nlm.nih.gov/25653233/

https://europepmc.org/article/MED/25653233

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4400529/

https://academic.oup.com/carcin/article/36/3/355/315383

https://www.researchgate.net/publication/272080901_Curcumin_mediates_chemosensitization_to_5-fluorouracil_through_miRNA-induced_suppression_of_epithelial-to-mesenchymal_transition_in_chemoresistant_colorectal_cancer


Keywords

  • bcm
  • BCM-95
  • bcm95
  • clinical study
  • colorectal cancer
  • curcugreen
  • Curcumin
  • research

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