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

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 tumo...

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Bibliographic Details
Published in:Anticancer research 2015-05, Vol.35 (5), p.2739-2746
Main Authors: Emoto, Makoto, Yano, Kyoko, Choijamts, Batsuren, Sakai, Shinnosuke, Hirasawa, Shun, Wakamori, Shinnosuke, Aizawa, Mamoru, Nabeshima, Kazuki, Tachibana, Katsuro, Kanomata, Nobuhiro
Format: Article
Language:English
Subjects:
Angiogenesis Inhibitors - administration & dosage
Animals
Carcinosarcoma - drug therapy
Carcinosarcoma - genetics
Carcinosarcoma - pathology
Cell Line, Tumor
Female
Humans
Mice
Neovascularization, Pathologic - drug therapy
Neovascularization, Pathologic - genetics
Neovascularization, Pathologic - pathology
Pyrrolidinones - administration & dosage
Spiro Compounds - administration & dosage
Uterine Neoplasms - drug therapy
Uterine Neoplasms - genetics
Uterine Neoplasms - pathology
Vascular Endothelial Growth Factor A - antagonists & inhibitors
Xenograft Model Antitumor Assays
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Summary: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.
ISSN:1791-7530