Details
- Autor(en) / Beteiligte
- Titel
- Synergistic effect of low-dose cucurbitacin B and low-dose methotrexate for treatment of human osteosarcoma
- Ist Teil von
- Cancer letters, 2011-07, Vol.306 (2), p.161-170
- Ort / Verlag
- Ireland: Elsevier Ireland Ltd
- Erscheinungsjahr
- 2011
- Link zum Volltext
- Quelle
- Elsevier ScienceDirect Journals
- Beschreibungen/Notizen
- Abstract We investigated the use of cucurbitacin B, a plant-derived tetracyclic triterpenoid, as a single agent or in combination with methotrexate (MTX) for human osteosarcoma (OS) treatment. Cucurbitacin B showed antiproliferative activity against seven human OS cell lines in vitro accompanying G2/M cell cycle arrest, apoptosis, and inhibition of ERK, Akt, and mTOR proteins. Cucurbitacin B in combination with MTX synergistically inhibited OS cell growth in vitro . Low-dose cucurbitacin B (LD-CuB, 0.5 mg/kg body weight) or low-dose MTX (LD-MTX, 150 mg/kg) failed to decrease the size of human OS xenografts in nude mice. However, combined therapy at identical concentrations inhibited tumor growth by 62% vs. LD-CuB and 81% vs. LD-MTX ( p < 0.001). Strikingly, the effect persisted even when the dose of MTX was decreased by two thirds (VLD-MTX, 50 mg/kg). In conclusion, cucurbitacin B alone or in combination with MTX shows promising antiproliferative activity against human OS.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0304-3835eISSN: 1872-7980DOI: 10.1016/j.canlet.2011.03.001Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4925102
- Format
- –
- Schlagworte
- Animals, Antimetabolites, Antineoplastic - therapeutic use, Apoptosis, Apoptosis - drug effects, Blotting, Western, body weight, Bone cancer, Bone Neoplasms - drug therapy, Bone Neoplasms - metabolism, Bone Neoplasms - pathology, Cancer therapies, cell cycle, Cell Cycle - drug effects, Cell growth, Cell Proliferation - drug effects, Chemical compounds, Chemotherapy, Cucurbitacin B, Dose-Response Relationship, Drug, Drug dosages, Drug Synergism, Female, Hematology, Oncology and Palliative Medicine, Humans, Immunoenzyme Techniques, Kinases, Life sciences, Methotrexate, Methotrexate - therapeutic use, Mice, Mice, Nude, Mitogen-Activated Protein Kinases - metabolism, Osteosarcoma, Osteosarcoma - drug therapy, Osteosarcoma - metabolism, Osteosarcoma - pathology, Phosphatidylinositol 3-Kinase - metabolism, Phosphorylation, Phosphorylation - drug effects, proteins, Proto-Oncogene Proteins c-akt - metabolism, Studies, Synergism, therapeutics, TOR Serine-Threonine Kinases - metabolism, Toxicity, Triterpenes - therapeutic use, Tumor Cells, Cultured, Xenograft, Xenograft Model Antitumor Assays