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In Vitro and In Vivo Antitumor Activity of a Novel Semisynthetic Derivative of Cucurbitacin B

Lung cancer is the most deadly type of cancer in humans, with non-small-cell lung cancer (NSCLC) being the most frequent and aggressive type of lung cancer showing high resistance to radiation and chemotherapy. Despite the outstanding progress made in anti-tumor therapy, discovering effective anti-tumor drugs is still a challenging task. Here we describe a new semisynthetic derivative of cucurbitacin B (DACE) as a potent inhibitor of NSCLC cell proliferation. DACE arrested the cell cycle of lung epithelial cells at the G2/M phase and induced cell apoptosis by interfering with EGFR activation and its downstream signaling, including AKT, ERK, and STAT3. Consistent with our in vitro studies, intraperitoneal application of DACE significantly suppressed the growth of mouse NSCLC that arises from type II alveolar pneumocytes due to constitutive expression of a human oncogenic c-RAF kinase (c-RAF-1-BxB) transgene in these cells. Taken together, these findings suggest that DACE is a promising lead compound for the development of an anti-lung-cancer drug.

Titel: In Vitro and In Vivo Antitumor Activity of a Novel Semisynthetic Derivative of Cucurbitacin B
Verfasser: Silva, Izabella T.
Carvalho, Annelise
Lang, Karen L.
Dudek, Sabine Eva GND
Masemann, Dörthe GND
Durán, Fernando J.
Caro, Miguel S. B.
Rapp, Ulf Rüdiger GND
Wixler, Viktor GND
Schenkel, Eloir P.
Simões, Cláudia M. O.
Ludwig, Stephan
Organisation: FB 13: Biologie
Dokumenttyp: Artikel
Medientyp: Text
Erscheinungsdatum: 12.02.2015
Publikation in MIAMI: 15.04.2015
Datum der letzten Änderung: 16.04.2019
Quelle: PLoS ONE 10 (2015) 2, e0117794, 1-19
Fachgebiete: Medizin und Gesundheit
Lizenz: CC BY 4.0
Sprache: Englisch
Anmerkungen: Finanziert durch den Open-Access-Publikationsfonds 2014/2015 der Deutschen Forschungsgemeinschaft (DFG) und der Westfälischen Wilhelms-Universität Münster (WWU Münster).
Format: PDF-Dokument
URN: urn:nbn:de:hbz:6-39299643678
DOI: 10.1371/journal.pone.0117794
ISSN: 1932-6203