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Buhrmann C, Shayan P, Banik K, et al. Targeting NF-κB Signaling by Calebin A, a Compound of Turmeric, in Multicellular Tumor Microenvironment: Potential Role of Apoptosis Induction in CRC Cells. Biomedicines. 2020;8(8)doi: 10.3390/biomedicines8080236.
Buhrmann, C., Shayan, P., Banik, K., Kunnumakkara, A. B., Kubatka, P., Koklesova, L., Shakibaei, M., & Su, J. Q. (2020). Targeting NF-κB Signaling by Calebin A, a Compound of Turmeric, in Multicellular Tumor Microenvironment: Potential Role of Apoptosis Induction in CRC Cells. Biomedicines, 8(8), . https://doi.org/10.3390/biomedicines8080236
Buhrmann, Constanze, et al. "Targeting NF-κB Signaling by Calebin A, a Compound of Turmeric, in Multicellular Tumor Microenvironment: Potential Role of Apoptosis Induction in CRC Cells." Biomedicines vol. 8,8 (2020). doi: https://doi.org/10.3390/biomedicines8080236
Buhrmann C, Shayan P, Banik K, Kunnumakkara AB, Kubatka P, Koklesova L, Shakibaei M, Su JQ. Targeting NF-κB Signaling by Calebin A, a Compound of Turmeric, in Multicellular Tumor Microenvironment: Potential Role of Apoptosis Induction in CRC Cells. Biomedicines. 2020 Jul 22;8(8). doi: 10.3390/biomedicines8080236. PMID: 32708030; PMCID: PMC7460490.
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Biomedicines. 2020 Jul 22;8(8). doi: 10.3390/biomedicines8080236.

Targeting NF-κB Signaling by Calebin A, a Compound of Turmeric, in Multicellular Tumor Microenvironment: Potential Role of Apoptosis Induction in CRC Cells.

Biomedicines

Constanze Buhrmann, Parviz Shayan, Kishore Banik, Ajaikumar B Kunnumakkara, Peter Kubatka, Lenka Koklesova, Mehdi Shakibaei, Su

Affiliations

  1. Musculoskeletal Research Group and Tumor Biology, Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilian-University Munich, Pettenkoferstrasse 11, D-80336 Munich, Germany.
  2. Department of Parasitology, Faculty of Veterinary Medicine, University of Tehran, Tehran 141556453, Iran.
  3. Cancer Biology Laboratory & DBT-AIST International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences & Bioengineering, Indian Institute of Technology Guwahati, Assam 781039, India.
  4. Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 03601 Martin, Slovakia.
  5. Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, 036 01 Martin, Slovakia.

PMID: 32708030 PMCID: PMC7460490 DOI: 10.3390/biomedicines8080236

Abstract

Increasing lines of evidence suggest that chronic inflammation mediates most chronic diseases, including cancer. The transcription factor, NF-κB, has been shown to be a major regulator of inflammation and metastasis in tumor cells. Therefore, compounds or any natural agents that can inhibit NF-κB activation have the potential to prevent and treat cancer. However, the mechanism by which Calebin A, a component of turmeric, regulates inflammation and disrupts the interaction between HCT116 colorectal cancer (CRC) cells and multicellular tumor microenvironment (TME) is still poorly understood. The 3D-alginate HCT116 cell cultures in TME were treated with Calebin A, BMS-345541, and dithiothreitol (DTT) and examined for invasiveness, proliferation, and apoptosis. The mechanism of TME-induced malignancy of cancer cells was confirmed by phase contrast, Western blotting, immunofluorescence, and DNA-binding assay. We found through DNA binding assay, that Calebin A inhibited TME-induced NF-κB activation in a dose-dependent manner. As a result of this inhibition, NF-κB phosphorylation and NF-κB nuclear translocation were down-modulated. Calebin A, or IκB-kinase (IKK) inhibitor (BMS-345541) significantly inhibited the direct interaction of nuclear p65 to DNA, and interestingly this interaction was reversed by DTT. Calebin A also suppressed the expression of NF-κB-promoted anti-apoptotic (Bcl-2, Bcl-xL, survivin), proliferation (Cyclin D1), invasion (MMP-9), metastasis (CXCR4), and down-regulated apoptosis (Caspase-3) gene biomarkers, leading to apoptosis in HCT116 cells. These results suggest that Calebin A can suppress multicellular TME-promoted CRC cell invasion and malignancy by inhibiting the NF-κB-promoting inflammatory pathway associated with carcinogenesis, underlining the potential of Calebin A for CRC treatment.

Keywords: Calebin A; NF-κB signaling; apoptosis; colorectal cancer; tumor microenvironment

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