STAT3 inhibitor, cucurbitacin I, is a novel therapeutic agent for osteosarcoma
| Autor: | Takao Matsubara, Takahiro Iino, Toru Oi, Yumiko Asanuma, Akihiko Matsumine, Yuki Yada, Akihiro Sudo, Mikinobu Goto, Kazuma Okuno, Takuya Kakimoto, Kunihiro Asanuma, Tomoki Nakamura |
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| Rok vydání: | 2016 |
| Předmět: |
STAT3 Transcription Factor
0301 basic medicine Cancer Research Cell Survival Survivin Cell Poly (ADP-Ribose) Polymerase-1 Mice Nude cucurbitacin I Antineoplastic Agents Apoptosis Bone Neoplasms Inhibitor of Apoptosis Proteins STAT3 Proto-Oncogene Proteins c-myc Mice 03 medical and health sciences 0302 clinical medicine In vivo osteosarcoma Cell Line Tumor medicine Animals Humans Cyclin D1 Viability assay Cell Proliferation biology Caspase 3 Cell growth Cell Cycle Articles Cell cycle Xenograft Model Antitumor Assays Triterpenes 030104 developmental biology medicine.anatomical_structure Oncology Cell culture 030220 oncology & carcinogenesis Cancer research biology.protein Myeloid Cell Leukemia Sequence 1 Protein Signal Transduction |
| Zdroj: | International Journal of Oncology |
| ISSN: | 1791-2423 1019-6439 |
| DOI: | 10.3892/ijo.2016.3757 |
| Popis: | The development of clinical agents remains a costly and time-consuming process. Although identification of new uses of existing drugs has been recognized as a more efficient approach for drug discovery than development of novel drugs, little screening of drugs that might be used for a rare malignant tumor such as osteosarcoma (OS) has been performed. In this study, we attempted to identify new molecular targeted agents for OS by employing Screening Committee of Anticancer Drugs (SCADS) kits. To screen compounds for OS treatment, their effect on cell viability of the OS cell lines 143B, MG63, HOS, SAOS-2, and HUO9 were evaluated. Candidate drugs were narrowed down based on a global anti-proliferative effect against these five OS cell lines. After excluding cytotoxic compounds and compounds unsuitable for in vivo administration, cucurbitacin I was extracted. Cucurbitacin I has been found to have cytotoxic and anti-proliferative properties against several tumors through inhibition of signal transducer and activator of transcription 3 (STAT3) activation. Cucurbitacin I dose- and time-dependently inhibited the proliferation of all five OS cell lines. Following cucurbitacin I treatment, STAT3 was inactivated and analysis of Mcl-1, cleaved PARP and caspase-3 indicated apoptosis induction. Expression of cell cycle regulator proteins, such as phospho-cyclin D1, c-Myc and survivin, were suppressed. Finally, cucurbitacin I potently inhibited the tumor growth of human OS 143B cells in nude mice. Our in vitro and in vivo results suggest that STAT3 inhibition by cucurbitacin I will be an effective and new approach for the treatment of OS. |
| Databáze: | OpenAIRE |
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