Display options
Cite
Buhrmann C, Kunnumakkara AB, Kumar A, et al. Multitargeting Effects of Calebin A on Malignancy of CRC Cells in Multicellular Tumor Microenvironment. Front Oncol. 2021;11:650603doi: 10.3389/fonc.2021.650603.
Buhrmann, C., Kunnumakkara, A. B., Kumar, A., Samec, M., Kubatka, P., Aggarwal, B. B., & Shakibaei, M. (2021). Multitargeting Effects of Calebin A on Malignancy of CRC Cells in Multicellular Tumor Microenvironment. Frontiers in oncology, 11650603. https://doi.org/10.3389/fonc.2021.650603
Buhrmann, Constanze, et al. "Multitargeting Effects of Calebin A on Malignancy of CRC Cells in Multicellular Tumor Microenvironment." Frontiers in oncology vol. 11 (2021): 650603. doi: https://doi.org/10.3389/fonc.2021.650603
Buhrmann C, Kunnumakkara AB, Kumar A, Samec M, Kubatka P, Aggarwal BB, Shakibaei M. Multitargeting Effects of Calebin A on Malignancy of CRC Cells in Multicellular Tumor Microenvironment. Front Oncol. 2021 Sep 29;11:650603. doi: 10.3389/fonc.2021.650603. eCollection 2021. PMID: 34660256; PMCID: PMC8511772.
Copy Download .nbib Format: NLM
Share it on

Front Oncol. 2021 Sep 29;11:650603. doi: 10.3389/fonc.2021.650603. eCollection 2021.

Multitargeting Effects of Calebin A on Malignancy of CRC Cells in Multicellular Tumor Microenvironment.

Frontiers in oncology

Constanze Buhrmann, Ajaikumar B Kunnumakkara, Aviral Kumar, Marek Samec, Peter Kubatka, Bharat B Aggarwal, Mehdi Shakibaei

Affiliations

  1. Musculoskeletal Research Group and Tumor Biology, Chair of Vegetative Anatomy, Institute of Anatomy, Faculty of Medicine, Ludwig-Maximilian-University Munich, Munich, Germany.
  2. Institute of Anatomy and Cell Biology, Faculty of Medicine, University of Augsburg, Augsburg, Germany.
  3. Cancer Biology Laboratory & Department of Biotechnology-National institute of Advanced Industrial Science and Technology (DBT-AIST) International Center for Translational and Environmental Research (DAICENTER), Department of Biosciences & Bioengineering, Indian Institute of Technology Guwahati, Assam, India.
  4. Department of Obstetrics and Gynecology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia.
  5. Department of Medical Biology, Jessenius Faculty of Medicine, Comenius University in Bratislava, Martin, Slovakia.
  6. Inflammation Research Center, San Diego, CA, United States.

PMID: 34660256 PMCID: PMC8511772 DOI: 10.3389/fonc.2021.650603

Abstract

BACKGROUND: Tumor microenvironment (TME) provides the essential prerequisite niche for promoting cancer progression and metastasis. Calebin A, a component of

METHODS: 3D-alginate tumor cultures (HCT116 cells) in the multicellular proinflammatory TME (fibroblast cells/T lymphocytes), tumor necrosis factor beta (TNF-β)-TME (fibroblast cells/TNF-β) were treated with/without Calebin A to address the pleiotropic actions of Calebin A in the CRC.

RESULTS: We found that Calebin A downmodulated proliferation, vitality, and migration of HCT116 cells in 3D-alginate cultures in multicellular proinflammatory TME or TNF-β-TME. In addition, Calebin A suppressed TNF-β-, similar to multicellular-TME-induced phosphorylation of nuclear factor kappa B (NF-κB) in a concentration-dependent manner. NF-κB-promoting proinflammatory mediators, associated with tumor growth and antiapoptotic molecules (i.e.,MMP-9, CXCR4, Ki-67, β1-integrin, and Caspase-3) and its translocation to the nucleus in HCT116 cells, were increased in both TME cultures. The multicellular-TME cultures further induced the survival of cancer stem cells (CSCs) (upregulation of CD133, CD44, and ALDH1). Last but not the least, Calebin A suppressed multicellular-, similar to TNF-β-TME-induced rigorous upregulation of NF-κB phosphorylation, various NF-κB-regulated gene products, CSCs activation, and survival in 3D-alginate tumor cultures.

CONCLUSIONS: The downmodulation of multicellular proinflammatory-, similar to TNF-β-TME-induced CRC proliferation, survival, and migration by the multitargeting agent Calebin A could be a new therapeutic strategy to suppress inflammation and CRC tumorigenesis.

Copyright © 2021 Buhrmann, Kunnumakkara, Kumar, Samec, Kubatka, Aggarwal and Shakibaei.

Keywords: Calebin A; NF-κB; T-lymphocyte; TNF-β; colorectal cancer; stromal cell; tumor microenvironment

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

References

  1. Cancer Sci. 2007 Mar;98(3):268-74 - PubMed
  2. Nutrients. 2018 Jul 12;10(7): - PubMed
  3. Biomaterials. 2010 Aug;31(22):5903-10 - PubMed
  4. Exp Biol Med (Maywood). 2019 Jan;244(1):1-12 - PubMed
  5. J Pathol Clin Res. 2018 Apr;4(2):124-134 - PubMed
  6. Oncogene. 2008 Oct 6;27(45):5904-12 - PubMed
  7. Adv Exp Med Biol. 2020;1226:1-22 - PubMed
  8. Cell Biol Int. 1997 Feb;21(2):75-86 - PubMed
  9. Int J Mol Sci. 2017 Jan 18;18(1): - PubMed
  10. Cell Stem Cell. 2014 Mar 6;14(3):275-91 - PubMed
  11. Front Biosci (Landmark Ed). 2019 Jun 1;24:1271-1283 - PubMed
  12. Antioxid Redox Signal. 2010 Sep 15;13(6):821-31 - PubMed
  13. Front Biosci. 2008 May 01;13:5094-107 - PubMed
  14. J Biol Chem. 2006 Jun 23;281(25):17023-17033 - PubMed
  15. J Vis Exp. 2015 Dec 28;(106):e53486 - PubMed
  16. Lancet. 2019 Oct 19;394(10207):1467-1480 - PubMed
  17. Int J Mol Sci. 2020 Mar 31;21(7): - PubMed
  18. Oncol Rep. 2010 Nov;24(5):1241-7 - PubMed
  19. Nat Rev Clin Oncol. 2017 Jul;14(7):399-416 - PubMed
  20. PLoS One. 2013 Jul 16;8(7):e69760 - PubMed
  21. World J Gastroenterol. 2004 Nov 15;10(22):3255-60 - PubMed
  22. J Biol Chem. 2014 Apr 25;289(17):11681-11694 - PubMed
  23. Gastroenterology. 2010 Jun;138(6):2151-62 - PubMed
  24. Front Immunol. 2020 Jan 15;10:3080 - PubMed
  25. Front Oncol. 2013 Apr 17;3:90 - PubMed
  26. PLoS One. 2017 Nov 2;12(11):e0186993 - PubMed
  27. J Cell Physiol. 2020 Nov;235(11):7696-7708 - PubMed
  28. Int J Cancer. 2019 Sep 1;145(5):1358-1370 - PubMed
  29. Curr Opin Pharmacol. 2009 Aug;9(4):351-69 - PubMed
  30. Proc Natl Acad Sci U S A. 1992 Oct 1;89(19):9064-8 - PubMed
  31. Nat Cell Biol. 2010 May;12(5):468-76 - PubMed
  32. Vaccines (Basel). 2020 Feb 06;8(1): - PubMed
  33. BMC Cancer. 2015 Apr 10;15:250 - PubMed
  34. Cell Cycle. 2013 Feb 1;12(3):480-90 - PubMed
  35. Curr Opin Genet Dev. 2008 Feb;18(1):3-10 - PubMed
  36. Expert Opin Drug Discov. 2008 Jan;3(1):1-10 - PubMed
  37. PLoS One. 2014 Sep 19;9(9):e107514 - PubMed
  38. Int J Mol Sci. 2019 Feb 15;20(4): - PubMed
  39. In Vitro Cell Dev Biol Anim. 2006 Sep-Oct;42(8-9):242-7 - PubMed
  40. Scand J Gastroenterol. 2013 May;48(5):563-9 - PubMed
  41. Healthcare (Basel). 2013 Dec 23;2(1):27-46 - PubMed
  42. Cold Spring Harb Perspect Biol. 2011 Mar 01;3(3): - PubMed
  43. Biomolecules. 2019 Jan 02;9(1): - PubMed
  44. Molecules. 2019 Mar 04;24(5): - PubMed
  45. Nat Rev Cancer. 2016 Aug 23;16(9):582-98 - PubMed
  46. Nat Rev Dis Primers. 2015 Nov 05;1:15065 - PubMed
  47. Biochem Pharmacol. 2006 Nov 30;72(11):1605-21 - PubMed
  48. Nat Rev Cancer. 2010 Jan;10(1):9-22 - PubMed
  49. Skin Pharmacol Physiol. 2009;22(2):114-21 - PubMed
  50. Front Immunol. 2018 Sep 27;9:2160 - PubMed
  51. Am J Physiol. 1999 Aug;277(2):C183-201 - PubMed
  52. Cell Physiol Biochem. 2017;42(1):145-155 - PubMed
  53. Neoplasia. 2015 Jan;17(1):1-15 - PubMed
  54. Curr Med Chem. 2021;28(22):4321-4342 - PubMed
  55. Cancer Treat Res. 2006;130:67-87 - PubMed
  56. Onco Targets Ther. 2018 Apr 11;11:2063-2073 - PubMed
  57. Nutrients. 2019 Dec 01;11(12): - PubMed
  58. Comput Struct Biotechnol J. 2018 Jul 27;16:279-287 - PubMed
  59. Blood. 2019 Mar 28;133(13):1489-1494 - PubMed
  60. CA Cancer J Clin. 2018 Nov;68(6):394-424 - PubMed
  61. Transl Oncol. 2009 Dec;2(4):321-8 - PubMed
  62. CA Cancer J Clin. 2020 May;70(3):145-164 - PubMed
  63. Mol Nutr Food Res. 2013 Sep;57(9):1510-28 - PubMed
  64. Phytomedicine. 2017 Oct 15;34:171-181 - PubMed
  65. J Clin Pathol. 2018 Feb;71(2):110-116 - PubMed
  66. Cell. 2010 Mar 19;140(6):883-99 - PubMed
  67. Biochem Pharmacol. 2002 Sep;64(5-6):883-8 - PubMed
  68. Gastroenterology. 2020 Jun;158(8):2072-2081 - PubMed
  69. Curr Pharm Biotechnol. 2009 Feb;10(2):192-6 - PubMed
  70. Cell Stem Cell. 2007 Oct 11;1(4):389-402 - PubMed
  71. Nutrients. 2019 Mar 26;11(3): - PubMed
  72. Onco Targets Ther. 2019 Dec 13;12:11033-11044 - PubMed
  73. Mol Nutr Food Res. 2013 Sep;57(9):1529-42 - PubMed
  74. Tumour Biol. 2013 Apr;34(2):735-41 - PubMed
  75. Blood. 2003 Feb 1;101(3):1053-62 - PubMed
  76. AMB Express. 2019 May 29;9(1):79 - PubMed
  77. Nat Rev Cancer. 2009 May;9(5):361-71 - PubMed

Publication Types