Azaspirene analogs inhibit the growth of human uterine carcinosarcoma in vitro and in vivo

Makoto Emoto, Kyoko Yano, Batsuren Choijamts, Shinnosuke Sakai, Shun Hirasawa, Shinnosuke Wakamori, Mamoru Aizawa, Kazuki Nabeshima, Katsuro Tachibana, Nobuhiro Kanomata

    Research output: Contribution to journalArticle

    6 Citations (Scopus)

    Abstract

    Uterine carcinosarcoma is a highly aggressive gynecological neoplasm that responds poorly to conventional chemotherapy and radiotherapy. Recent studies have shown high angiogenic activities of this tumor, hence anti-angiogenic approaches are expected to provide new treatment strategies for this tumor. In previous work, azaspirene was isolated from Neosartorya sp. fungi, and in vitro anti-angiogenic activities were shown. In the present study, the anti-angiogenic effects of azaspirene analogs, synthetic molecules with a shorter ethyl group replacing a hexadienyl side-chain of the natural compound, were assessed in vitro using human umbilical vein endothelial cells (HUVECs) co-cultured with FU-MMT-3 human uterine carcinosarcoma cells. The anti-tumor and anti-angiogenic effects of these analogs were also evaluated in vivo using FU-MMT-3 xenografted tumors in nude mice. The azaspirene analogs inhibited the tube formation of HUVECs induced by FU-MMT-3 cells in vitro and significantly suppressed tumor growth in vivo compared to the untreated group (control). A significant reduction of the microvessel density in tumors was observed, in comparison to the control. No apparent toxicity, including body loss, was observed in any mice treated in this study. These azaspirene analogs may be effective against uterine carcinosarcoma, possibly acting via potent anti-angiogenic effects.

    Original languageEnglish
    Pages (from-to)2739-2746
    Number of pages8
    JournalAnticancer Research
    Volume35
    Issue number5
    Publication statusPublished - 2015 May 1

    Fingerprint

    Carcinosarcoma
    Growth
    Neoplasms
    Human Umbilical Vein Endothelial Cells
    Neosartorya
    Microvessels
    In Vitro Techniques
    azaspirene
    Nude Mice
    Fungi
    Radiotherapy
    Drug Therapy
    Control Groups

    Keywords

    • Anti-angiogenic therapy
    • Azaspirene
    • Uterine carcinosarcoma

    ASJC Scopus subject areas

    • Cancer Research
    • Oncology

    Cite this

    Emoto, M., Yano, K., Choijamts, B., Sakai, S., Hirasawa, S., Wakamori, S., ... Kanomata, N. (2015). Azaspirene analogs inhibit the growth of human uterine carcinosarcoma in vitro and in vivo. Anticancer Research, 35(5), 2739-2746.

    Azaspirene analogs inhibit the growth of human uterine carcinosarcoma in vitro and in vivo. / Emoto, Makoto; Yano, Kyoko; Choijamts, Batsuren; Sakai, Shinnosuke; Hirasawa, Shun; Wakamori, Shinnosuke; Aizawa, Mamoru; Nabeshima, Kazuki; Tachibana, Katsuro; Kanomata, Nobuhiro.

    In: Anticancer Research, Vol. 35, No. 5, 01.05.2015, p. 2739-2746.

    Research output: Contribution to journalArticle

    Emoto, M, Yano, K, Choijamts, B, Sakai, S, Hirasawa, S, Wakamori, S, Aizawa, M, Nabeshima, K, Tachibana, K & Kanomata, N 2015, 'Azaspirene analogs inhibit the growth of human uterine carcinosarcoma in vitro and in vivo', Anticancer Research, vol. 35, no. 5, pp. 2739-2746.
    Emoto M, Yano K, Choijamts B, Sakai S, Hirasawa S, Wakamori S et al. Azaspirene analogs inhibit the growth of human uterine carcinosarcoma in vitro and in vivo. Anticancer Research. 2015 May 1;35(5):2739-2746.
    Emoto, Makoto ; Yano, Kyoko ; Choijamts, Batsuren ; Sakai, Shinnosuke ; Hirasawa, Shun ; Wakamori, Shinnosuke ; Aizawa, Mamoru ; Nabeshima, Kazuki ; Tachibana, Katsuro ; Kanomata, Nobuhiro. / Azaspirene analogs inhibit the growth of human uterine carcinosarcoma in vitro and in vivo. In: Anticancer Research. 2015 ; Vol. 35, No. 5. pp. 2739-2746.
    @article{921d2d3ebe514786b07a0744ae0ece1a,
    title = "Azaspirene analogs inhibit the growth of human uterine carcinosarcoma in vitro and in vivo",
    abstract = "Uterine carcinosarcoma is a highly aggressive gynecological neoplasm that responds poorly to conventional chemotherapy and radiotherapy. Recent studies have shown high angiogenic activities of this tumor, hence anti-angiogenic approaches are expected to provide new treatment strategies for this tumor. In previous work, azaspirene was isolated from Neosartorya sp. fungi, and in vitro anti-angiogenic activities were shown. In the present study, the anti-angiogenic effects of azaspirene analogs, synthetic molecules with a shorter ethyl group replacing a hexadienyl side-chain of the natural compound, were assessed in vitro using human umbilical vein endothelial cells (HUVECs) co-cultured with FU-MMT-3 human uterine carcinosarcoma cells. The anti-tumor and anti-angiogenic effects of these analogs were also evaluated in vivo using FU-MMT-3 xenografted tumors in nude mice. The azaspirene analogs inhibited the tube formation of HUVECs induced by FU-MMT-3 cells in vitro and significantly suppressed tumor growth in vivo compared to the untreated group (control). A significant reduction of the microvessel density in tumors was observed, in comparison to the control. No apparent toxicity, including body loss, was observed in any mice treated in this study. These azaspirene analogs may be effective against uterine carcinosarcoma, possibly acting via potent anti-angiogenic effects.",
    keywords = "Anti-angiogenic therapy, Azaspirene, Uterine carcinosarcoma",
    author = "Makoto Emoto and Kyoko Yano and Batsuren Choijamts and Shinnosuke Sakai and Shun Hirasawa and Shinnosuke Wakamori and Mamoru Aizawa and Kazuki Nabeshima and Katsuro Tachibana and Nobuhiro Kanomata",
    year = "2015",
    month = "5",
    day = "1",
    language = "English",
    volume = "35",
    pages = "2739--2746",
    journal = "Anticancer Research",
    issn = "0250-7005",
    publisher = "International Institute of Anticancer Research",
    number = "5",

    }

    TY - JOUR

    T1 - Azaspirene analogs inhibit the growth of human uterine carcinosarcoma in vitro and in vivo

    AU - Emoto, Makoto

    AU - Yano, Kyoko

    AU - Choijamts, Batsuren

    AU - Sakai, Shinnosuke

    AU - Hirasawa, Shun

    AU - Wakamori, Shinnosuke

    AU - Aizawa, Mamoru

    AU - Nabeshima, Kazuki

    AU - Tachibana, Katsuro

    AU - Kanomata, Nobuhiro

    PY - 2015/5/1

    Y1 - 2015/5/1

    N2 - Uterine carcinosarcoma is a highly aggressive gynecological neoplasm that responds poorly to conventional chemotherapy and radiotherapy. Recent studies have shown high angiogenic activities of this tumor, hence anti-angiogenic approaches are expected to provide new treatment strategies for this tumor. In previous work, azaspirene was isolated from Neosartorya sp. fungi, and in vitro anti-angiogenic activities were shown. In the present study, the anti-angiogenic effects of azaspirene analogs, synthetic molecules with a shorter ethyl group replacing a hexadienyl side-chain of the natural compound, were assessed in vitro using human umbilical vein endothelial cells (HUVECs) co-cultured with FU-MMT-3 human uterine carcinosarcoma cells. The anti-tumor and anti-angiogenic effects of these analogs were also evaluated in vivo using FU-MMT-3 xenografted tumors in nude mice. The azaspirene analogs inhibited the tube formation of HUVECs induced by FU-MMT-3 cells in vitro and significantly suppressed tumor growth in vivo compared to the untreated group (control). A significant reduction of the microvessel density in tumors was observed, in comparison to the control. No apparent toxicity, including body loss, was observed in any mice treated in this study. These azaspirene analogs may be effective against uterine carcinosarcoma, possibly acting via potent anti-angiogenic effects.

    AB - Uterine carcinosarcoma is a highly aggressive gynecological neoplasm that responds poorly to conventional chemotherapy and radiotherapy. Recent studies have shown high angiogenic activities of this tumor, hence anti-angiogenic approaches are expected to provide new treatment strategies for this tumor. In previous work, azaspirene was isolated from Neosartorya sp. fungi, and in vitro anti-angiogenic activities were shown. In the present study, the anti-angiogenic effects of azaspirene analogs, synthetic molecules with a shorter ethyl group replacing a hexadienyl side-chain of the natural compound, were assessed in vitro using human umbilical vein endothelial cells (HUVECs) co-cultured with FU-MMT-3 human uterine carcinosarcoma cells. The anti-tumor and anti-angiogenic effects of these analogs were also evaluated in vivo using FU-MMT-3 xenografted tumors in nude mice. The azaspirene analogs inhibited the tube formation of HUVECs induced by FU-MMT-3 cells in vitro and significantly suppressed tumor growth in vivo compared to the untreated group (control). A significant reduction of the microvessel density in tumors was observed, in comparison to the control. No apparent toxicity, including body loss, was observed in any mice treated in this study. These azaspirene analogs may be effective against uterine carcinosarcoma, possibly acting via potent anti-angiogenic effects.

    KW - Anti-angiogenic therapy

    KW - Azaspirene

    KW - Uterine carcinosarcoma

    UR - http://www.scopus.com/inward/record.url?scp=84929678391&partnerID=8YFLogxK

    UR - http://www.scopus.com/inward/citedby.url?scp=84929678391&partnerID=8YFLogxK

    M3 - Article

    VL - 35

    SP - 2739

    EP - 2746

    JO - Anticancer Research

    JF - Anticancer Research

    SN - 0250-7005

    IS - 5

    ER -