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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

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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.

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Acknowledgments

We thank Mr Makoto Nishimori, Satoshi Tomiyasu, Susumu Kobayakawa, Shinichi Tanaka, and Mrs Naoko Yasumura (Graduate School of Science and Industrial Technology, Kurashiki University of Science and the Arts) for their contributions to this study.

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Authors and Affiliations

  1. Department of Chemical Technology, Graduate School of Science and Industrial Technology, Kurashiki University of Science and the Arts, Kurashiki, Okayama, Japan

    Michihiro Mori, Takuya Sakaguchi & Eiji Ohno

  2. Department of Medical Life Science, College of Life Science, Kurashiki University of Science and the Arts, 2640 Nishinoura Tsurajima-cho, Kurashiki-shi, Okayama, Japan

    Michihiro Mori, Tomoyuki Miyamoto, Hiromasa Yakushiji, Setsuyo Ohno, Yasuyuki Miyake, Takuya Sakaguchi & Eiji Ohno

  3. Kake Institute of Cytopathology, Kurashiki, Okayama, Japan

    Tomoyuki Miyamoto, Setsuyo Ohno, Yasuyuki Miyake, Takuya Sakaguchi & Eiji Ohno

  4. Department of Clinical Cytology, School of Allied Health Sciences, Kitasato University, Sagamihara, Kanagawa, Japan

    Manabu Hattori

  5. Department of Obstetrics and Gynecology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Okayama, Japan

    Atsushi Hongo

  6. Department of Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Kyoto, Japan

    Akihiko Nakaizumi

  7. Department of Cytopathology and Gynecology, Osaka Cancer Prevention and Detection Center, Osaka, Osaka, Japan

    Masatsugu Ueda

Authors
  1. Michihiro Mori
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  2. Tomoyuki Miyamoto
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  3. Hiromasa Yakushiji
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  5. Yasuyuki Miyake
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  6. Takuya Sakaguchi
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  7. Manabu Hattori
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  8. Atsushi Hongo
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  9. Akihiko Nakaizumi
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  10. Masatsugu Ueda
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  11. Eiji Ohno
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Correspondence to Michihiro Mori.

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Mori, M., Miyamoto, T., Yakushiji, H. et al. 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. Human Cell 25, 9–15 (2012). https://doi.org/10.1007/s13577-011-0038-8

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  • DOI: https://doi.org/10.1007/s13577-011-0038-8

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