In vitro and in vivo antitumor activity of a novel semisynthetic derivative of cucurbitacin B
Autor: | Izabella T, Silva, Annelise, Carvalho, Karen L, Lang, Sabine E, Dudek, Dörthe, Masemann, Fernando J, Durán, Miguel S B, Caro, Ulf R, Rapp, Viktor, Wixler, Eloir P, Schenkel, Cláudia M O, Simões, Stephan, Ludwig |
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Rok vydání: | 2014 |
Předmět: |
Male
STAT3 Transcription Factor Lung Neoplasms Antineoplastic Agents Apoptosis Mice Transgenic Mice Phosphatidylinositol 3-Kinases Carcinoma Non-Small-Cell Lung Cell Line Tumor Animals Humans Phosphorylation Cytoskeleton Tumor Stem Cell Assay Cell Proliferation Caspase 3 Cell Cycle Checkpoints Xenograft Model Antitumor Assays Triterpenes respiratory tract diseases ErbB Receptors Disease Models Animal raf Kinases Apoptosis Regulatory Proteins Proto-Oncogene Proteins c-akt Signal Transduction Research Article |
Zdroj: | PLoS ONE |
ISSN: | 1932-6203 |
Popis: | 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. |
Databáze: | OpenAIRE |
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