Activator protein-1 inhibition by 3-[(dodecylthiocarbonyl)methyl]-glutamaride impairs invasion and radiosensitizes osteosarcoma cells in vitro.
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.
1 Division of Pediatric Oncology, Department of Pediatrics, Faculty of Medicine of Ribeirão Preto, University of São Paulo , Ribeirão Preto, Brazil .
María Sol
MS
Brassesco
Julia Alejandra
JA
Pezuk
Jaqueline Carvalho
JC
de Oliveira
Elvis Terci
ET
Valera
Harley Francisco
HF
de Oliveira
Carlos Alberto
CA
Scrideli
Kazuo
K
Umezawa
Luiz Gonzaga
LG
Tone
D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004357:Drug Synergism; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D009361:Neoplasm Invasiveness / Q000473:pathology; D012516:Osteosarcoma / Q000188:drug therapy* / Q000532:radiotherapy; D010881:Piperidones / Q000494:pharmacology*; D011836:Radiation Tolerance / Q000187:drug effects*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*; D014410:Tumor Stem Cell Assay; D000098853:Podoplanin
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin; D020778:Matrix Metalloproteinase 2; D008562:Membrane Glycoproteins; D010881:Piperidones; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D018808:Transcription Factor AP-1; C573776:3-((dodecylthiocarbonyl)methyl)glutarimide; C117468:PDPN protein, human; D000098853:Podoplanin; C560822:TIMP1 protein, human; C560823:TIMP2 protein, human
AP-1; DTCM-g; osteosarcoma; radiation; treatment