Histone acetyltransferase p300/CBP inhibitor C646 blocks the survival and invasion pathways of gastric cancer cell lines

  • Authors:
    • Ya-Mei Wang
    • Meng-Li Gu
    • Fan-Sheng Meng
    • Wen-Rui Jiao
    • Xin-Xin Zhou
    • Hang-Ping Yao
    • Feng Ji
  • View Affiliations

  • Published online on: October 23, 2017     https://doi.org/10.3892/ijo.2017.4176
  • Pages:1860-1868
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Abstract

The histone acetyltransferases (HATs) adenovirus E1A-associated protein (p300) and CREB binding protein (CBP) serve as coactivators during a diverse assortment of cellular processes. In the present study, p300 and CBP were highly expressed in 5 gastric cancer (GC) cell lines (SGC‑7901, MKN45, MGC-803, BGC-823 and KATO III) compared with human normal gastric epithelial cell line (GES-1). C646, a selective inhibitor of p300 and CBP, inhibited cell viability and cell cycle and promoted cell apoptosis in all 5 GC cell lines. In addition, C646 suppressed the migration and invasion capability of the GC cell lines, except for the middle-differentiated SGC-7901 cell line. Furthermore, we detected the differential expression of corresponding oncogenic signalling molecules, such as c-Met, Akt, Bcl-2, Bax, cyclin D1, MMP7 and MMP9, in GC cells following C646 treatment. In conclusion, our results suggest that C646 inhibits the acetylation of histone H3 via inactivation of p300 and CBP, resulting in antineoplastic effects toward GC cells. Thus, the selective HAT inhibitor C646 could be a promising antitumour reagent for GC treatment.

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December 2017
Volume 51 Issue 6

Print ISSN: 1019-6439
Online ISSN:1791-2423

2016 Impact Factor: 3.079
Ranked #33/217 Oncology
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APA
Wang, Y., Gu, M., Meng, F., Jiao, W., Zhou, X., Yao, H., & Ji, F. (2017). Histone acetyltransferase p300/CBP inhibitor C646 blocks the survival and invasion pathways of gastric cancer cell lines. International Journal of Oncology, 51, 1860-1868. https://doi.org/10.3892/ijo.2017.4176
MLA
Wang, Y., Gu, M., Meng, F., Jiao, W., Zhou, X., Yao, H., Ji, F."Histone acetyltransferase p300/CBP inhibitor C646 blocks the survival and invasion pathways of gastric cancer cell lines". International Journal of Oncology 51.6 (2017): 1860-1868.
Chicago
Wang, Y., Gu, M., Meng, F., Jiao, W., Zhou, X., Yao, H., Ji, F."Histone acetyltransferase p300/CBP inhibitor C646 blocks the survival and invasion pathways of gastric cancer cell lines". International Journal of Oncology 51, no. 6 (2017): 1860-1868. https://doi.org/10.3892/ijo.2017.4176