Human Cell

, Volume 25, Issue 1, pp 9–15

Effects of N-[N-(3, 5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester (DAPT) on cell proliferation and apoptosis in Ishikawa endometrial cancer cells

  • Michihiro Mori
  • Tomoyuki Miyamoto
  • Hiromasa Yakushiji
  • Setsuyo Ohno
  • Yasuyuki Miyake
  • Takuya Sakaguchi
  • Manabu Hattori
  • Atsushi Hongo
  • Akihiko Nakaizumi
  • Masatsugu Ueda
  • Eiji Ohno
Research Article

DOI: 10.1007/s13577-011-0038-8

Cite this article as:
Mori, M., Miyamoto, T., Yakushiji, H. et al. Human Cell (2012) 25: 9. doi:10.1007/s13577-011-0038-8

Abstract

Endometrial cancer is one of the most common gynecological malignancies in Japan, where the disease shows an increasing morbidity. However, surgical therapy remains the treatment of choice for endometrial cancers that tend to be insensitive to radiation therapy and chemotherapy. Therefore, novel therapeutic strategies are required. The Notch signaling pathway regulates embryogenesis and cellular development, but deregulated Notch signaling may contribute to tumorigenesis in several cancers. Moreover, γ-secretase inhibitors have been shown to be potent inhibitors of the Notch signaling pathway; they suppress cellular proliferation and induce apoptosis in several cancer cells. In the present study, we investigated the effect of N-[N-(3, 5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester (DAPT, γ-secretase inhibitor) on the cell proliferation and apoptosis in Ishikawa endometrial cancer cells. Real-time PCR detected mRNA derived from NOTCH1 and HES1, which are target genes of the Notch signaling pathway, in Ishikawa endometrial cancer cells. After blocking Notch signaling, cellular proliferation decreased, accompanied by increased expression of p21 mRNA and decreased expression of the cyclin A protein. Furthermore, blockade of Notch signaling induced apoptosis. These results suggest that the Notch signaling pathway may be involved in cell proliferation through cell cycle regulation and apoptosis in Ishikawa endometrial cancer cells. Inhibition of the Notch signaling pathway by γ-secretase inhibitors is expected to be a potential target of novel therapeutic strategies for endometrial cancer.

Keywords

Apoptosis Cell proliferation Endometrial neoplasms N-[N-(3, 5-difluorophenacetyl-l-alanyl)]-S-phenylglycine t-butyl ester Notch1 

Copyright information

© Japan Human Cell Society and Springer 2011

Authors and Affiliations

  • Michihiro Mori
    • 1
    • 2
  • Tomoyuki Miyamoto
    • 2
    • 3
  • Hiromasa Yakushiji
    • 2
  • Setsuyo Ohno
    • 2
    • 3
  • Yasuyuki Miyake
    • 2
    • 3
  • Takuya Sakaguchi
    • 1
    • 2
    • 3
  • Manabu Hattori
    • 4
  • Atsushi Hongo
    • 5
  • Akihiko Nakaizumi
    • 6
  • Masatsugu Ueda
    • 7
  • Eiji Ohno
    • 1
    • 2
    • 3
  1. 1.Department of Chemical Technology, Graduate School of Science and Industrial TechnologyKurashiki University of Science and the ArtsKurashikiJapan
  2. 2.Department of Medical Life Science, College of Life ScienceKurashiki University of Science and the ArtsKurashiki-shiJapan
  3. 3.Kake Institute of CytopathologyKurashikiJapan
  4. 4.Department of Clinical Cytology, School of Allied Health SciencesKitasato UniversitySagamiharaJapan
  5. 5.Department of Obstetrics and GynecologyOkayama University Graduate School of Medicine, Dentistry and Pharmaceutical SciencesOkayamaJapan
  6. 6.Department of Human Health Sciences, Graduate School of MedicineKyoto UniversityKyotoJapan
  7. 7.Department of Cytopathology and GynecologyOsaka Cancer Prevention and Detection CenterOsakaJapan

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