1. Academic Validation
  2. Microsatellite Status and IκBα Expression Levels Predict Sensitivity to Pharmaceutical Curcumin in Colorectal Cancer Cells

Microsatellite Status and IκBα Expression Levels Predict Sensitivity to Pharmaceutical Curcumin in Colorectal Cancer Cells

  • Cancers (Basel). 2022 Feb 17;14(4):1032. doi: 10.3390/cancers14041032.
Lili Lu 1 Randy Przybylla 1 Yuru Shang 1 Meng Dai 1 Mathias Krohn 1 Oliver Holger Krämer 2 Christina Susanne Mullins 1 Michael Linnebacher 1
Affiliations

Affiliations

  • 1 Department of General Surgery, Molecular Oncology and Immunotherapy, Rostock University Medical Center, 18057 Rostock, Germany.
  • 2 Institute of Toxicology, Mainz University Medical Center, 55131 Mainz, Germany.
Abstract

Clinical utilization of curcumin in colorectal Cancer (CRC) was revived as a result of the development of novel curcumin formulations with improved bioavailability. Additionally, identification of biomarkers for curcumin sensitivity would also promote successful clinical applications. Here, we wanted to identify such biomarkers in order to establish a predictive model for curcumin sensitivity. Thirty-two low-passage CRC cell lines with specified tumor characteristics were included. Curcumin suppressed cell proliferation, yet sensitivity levels were distinct. Most curcumin-sensitive CRC cell lines were microsatellite stable and expressed high levels of IκBα. The predictive capacity of this biomarker combination possessed a statistical significance of 72% probability to distinguish correctly between curcumin-sensitive and -resistant CRC cell lines. Detailed functional analyses were performed with three sensitive and three resistant CRC cell lines. As curcumin's mode of action, inhibition of NF-κB p65 activation via IκBα was identified. In consequence, we hypothesize that novel curcumin formulations-either alone or, more likely, in combination with standard therapeutics-can be expected to prove clinically beneficial for CRC patients with high IκBα expression levels.

Keywords

CXCL-1; IL-8; IκBα; NF-κB p65; biomarker; colorectal cancer; curcumin; microsatellite instability; microsatellite stability; sensitivity.

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