Induction of a less aggressive phenotype in human colon carcinoma HCT116 cells by chronic exposure to HDAC inhibitor SAHA

  • Authors:
    • Alessandro Bressan
    • Mario Bigioni
    • Daniela Bellarosa
    • Federica Nardelli
    • Clelia Irrissuto
    • Carlo Alberto Maggi
    • Monica Binaschi
  • View Affiliations

  • Published online on: November 1, 2010     https://doi.org/10.3892/or_00000979
  • Pages: 1249-1255
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Abstract

Histone deacetylase inhibitors (HDACis) are anticancer molecules that epigenetically modulate cell functions. Chronic exposure of HCT116 colon cancer cells to SAHA has been investigated for a better understanding of resistance mechanisms but, surprisingly, a less aggressive tumor phenotype both in vitro and in vivo was obtained after exposure to increasing concentrations of SAHA. Indeed, HCT116/SAHA cells when injected into nude mice showed a reduced engraftment and growth with respect to HCT116 cells. This difference was not observed inoculating the cells into NOD/SCID mice that, differently from nude mice, lack NK activity, thus suggesting the involvement of the native immune response in impairment of HCT116/SAHA cell growth. In agreement with this result, a growing induction of NKG2D ligand expression, MICA and MICB, that are molecular mediators of NK cell killing, was confirmed in HCT116/SAHA chronically exposed to SAHA. A reduced clonogenic efficiency was also observed in HCT116/SAHA with respect to HCT116 cells. Interestingly, even after chronic exposure to SAHA, HCT116/SAHA cells developed only a moderate resistance to SAHA both in vitro and in vivo and they acquired a collateral sensitivity to anthracyclines. These results are of note and probably rely on the fact that, having simultaneously many different targets, HDACis would require many different mutations to display high resistance index. Moreover, to understand the molecular basis of HCT116/SAHA cell phenotype a gene expression profile of cancer genes was evaluated in HCT116 incubated with SAHA for 24 h and in HCT116/SAHA cells to identify selectively regulated genes.

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November 2010
Volume 24 Issue 5

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Bressan A, Bigioni M, Bellarosa D, Nardelli F, Irrissuto C, Maggi CA and Binaschi M: Induction of a less aggressive phenotype in human colon carcinoma HCT116 cells by chronic exposure to HDAC inhibitor SAHA . Oncol Rep 24: 1249-1255, 2010
APA
Bressan, A., Bigioni, M., Bellarosa, D., Nardelli, F., Irrissuto, C., Maggi, C.A., & Binaschi, M. (2010). Induction of a less aggressive phenotype in human colon carcinoma HCT116 cells by chronic exposure to HDAC inhibitor SAHA . Oncology Reports, 24, 1249-1255. https://doi.org/10.3892/or_00000979
MLA
Bressan, A., Bigioni, M., Bellarosa, D., Nardelli, F., Irrissuto, C., Maggi, C. A., Binaschi, M." Induction of a less aggressive phenotype in human colon carcinoma HCT116 cells by chronic exposure to HDAC inhibitor SAHA ". Oncology Reports 24.5 (2010): 1249-1255.
Chicago
Bressan, A., Bigioni, M., Bellarosa, D., Nardelli, F., Irrissuto, C., Maggi, C. A., Binaschi, M." Induction of a less aggressive phenotype in human colon carcinoma HCT116 cells by chronic exposure to HDAC inhibitor SAHA ". Oncology Reports 24, no. 5 (2010): 1249-1255. https://doi.org/10.3892/or_00000979