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

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    8 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

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    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., 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, 35(5), 2739-2746.