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Cancer Biother Radiopharm. 2013 May;28(4):351-8. doi: 10.1089/cbr.2012.1305. Epub 2013 Jan 25.

Activator protein-1 inhibition by 3-[(dodecylthiocarbonyl)methyl]-glutamaride impairs invasion and radiosensitizes osteosarcoma cells in vitro.

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1 Division of Pediatric Oncology, Department of Pediatrics, Faculty of Medicine of Ribeirão Preto, University of São Paulo , Ribeirão Preto, Brazil .


Osteosarcoma (OS) is the most common primary malignant bone tumor. Despite advances in neoadjuvant multi-agent chemotherapy, the outcome of patients has not significantly improved in the last decades, making the search for more effective therapeutic agents imperative. In the present study, we explored the possibility of using activator protein-1 inhibition by 3-[(dodecylthiocarbonyl)methyl]-glutarimide (DTCM-g) as a new therapeutic strategy in two OS cell lines, HOS and MG-63. Our results showed that low concentrations (2.5, 5, 10, and 20 μg/mL) of the drug significantly decreased cell proliferation and clonogenic capacity, albeit it did not significantly induce cell death. DTCM-g also decreased cell invasiveness, and inhibited PDPN, MMP-2, TIMP1, and TIMP2 expressions. Moreover, our results showed that DTCM-g synergized with ionizing radiation in both cell lines while chemosensitized MG-63 cells to doxorubicin treatment. Even though additional laboratorial and preclinical tests are still needed to support our data, we demonstrate that DTCM-g inhibits growth in OS cells, increases the cytotoxicity of other commonly used agents, and may possess antimetastatic activity.


AP-1; DTCM-g; osteosarcoma; radiation; treatment

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