FR901228, a novel histone deacetylase inhibitor, induces cell cycle arrest and subsequent apoptosis in refractory human pancreatic cancer cells

  • Authors:
    • Nariatsu Sato
    • Tetsuo Ohta
    • Hirohisa Kitagawa
    • Masato Kayahara
    • Itasu Ninomiya
    • Sachio Fushida
    • Takashi Fujimura
    • Gen-Ichi Nishimura
    • Koichi Shimizu
    • Koichi Miwa
  • View Affiliations

  • Published online on: March 1, 2004     https://doi.org/10.3892/ijo.24.3.679
  • Pages: 679-685
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Histone deacetylase (HDAC) inhibitors have antiproliferative activity against human cancer cells via cell cycle arrest, differentiation, and apoptosis. However, no report has focused on the apoptotic potential of HDAC inhibitors in refractory human pancreatic cancer. This study was designed to examine the apoptotic potential of FR901228, a novel HDAC inhibitor, in five human pancreatic cancer cell lines: Capan-1, BxPC-3, HPAF, Panc-1, and MIAPaCa-2. FR901228 markedly inhibited the proliferation of all five cell lines (IC50: 1-500 nM), with the greatest effect in MIAPaCa-2 cells. Treatment of each cell line with FR901228 (10-100 nM) caused cell cycle arrest at the G1 or G2/M phase and subsequent apoptosis. FR901228 induced expression of hyperacetylated histone H3 after 3 h of treatment and overexpression of p21Waf-1 after 6 h. In addition, FR901228 induced apoptosis by activating caspase-3, which led to cleavage of p21Waf-1 into a 15-kDa breakdown product and drove cancer cells from cell cycle arrest into apoptosis. FR901228 also decreased the protein level of survivin dramatically. Our results show that FR901228 markedly inhibits the growth of pancreatic cancer cells, not only through cell cycle arrest, but also through subsequent apoptosis; this was accompanied by caspase-3 activation, survivin degradation, and p21Waf-1 cleavage. FR901228 may prove clinically useful as an agent for refractory pancreatic cancers.

Related Articles

Journal Cover

March 2004
Volume 24 Issue 3

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

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Sato, N., Ohta, T., Kitagawa, H., Kayahara, M., Ninomiya, I., Fushida, S. ... Miwa, K. (2004). FR901228, a novel histone deacetylase inhibitor, induces cell cycle arrest and subsequent apoptosis in refractory human pancreatic cancer cells. International Journal of Oncology, 24, 679-685. https://doi.org/10.3892/ijo.24.3.679
MLA
Sato, N., Ohta, T., Kitagawa, H., Kayahara, M., Ninomiya, I., Fushida, S., Fujimura, T., Nishimura, G., Shimizu, K., Miwa, K."FR901228, a novel histone deacetylase inhibitor, induces cell cycle arrest and subsequent apoptosis in refractory human pancreatic cancer cells". International Journal of Oncology 24.3 (2004): 679-685.
Chicago
Sato, N., Ohta, T., Kitagawa, H., Kayahara, M., Ninomiya, I., Fushida, S., Fujimura, T., Nishimura, G., Shimizu, K., Miwa, K."FR901228, a novel histone deacetylase inhibitor, induces cell cycle arrest and subsequent apoptosis in refractory human pancreatic cancer cells". International Journal of Oncology 24, no. 3 (2004): 679-685. https://doi.org/10.3892/ijo.24.3.679